The following are pertinent references that may be helpful for doctors or patients suffering from Parkinson's or Parkinsonian Syndromes. 

Current Alternative Research Relating to Parkinson's

Thompson, M.; Thompson, L.; Combined Neurofeedback and Biofeedback for Dystonia and Parkinson's Disease: Theory and Case in ProgressJournal of Neurotherapy. 2002 Spr; 6/1: 100-102
ABSTRACT: This paper presents a theoretical framework for using a combination of neurofeedback and biofeedback with clients who have dystonia (or a combination of dystonia and Parkinson's Disease). Initial work has demonstrated promising results in terms of symptom relief and an improvement in the quality oflife.

Thompson, M.; Thompson, L.; Biofeedback for Movement Disorders (Dystonia with Parkinson's Disease): Theory and Preliminary Journal of Neurotherapy. 2002 Win; 6/4: 51-70
ABSTRACT:  Background: This paper presents a theoretical framework for using a combination of EEG biofeedback plus regular biofeedback with clients who have movement disorders. Method: A case study is included that describes intervention and results with a 47-year-old woman with the dual diagnosis of Parkinson's disease and dystonia. The rational for adding biofeedback interventions to traditional medical treatment hinges on the fact that muscle spindles, which are involved in muscle movement and tone, have double innervations, cholinergic and sympathetic (Passatore, Grassi,& Filippi, 1985). Both of these systems can be operantly conditioned using biofeedback. There
were two learning goals: (1) increase the production of 12 to 15 Hzactivity since this sensor motor rhythm (SMR) is associated with decreasedfiring of the red nucleus and the red nucleus, in turn, has links to themuscle spindles (Sterman, 2000); (2) train for calm, relaxed autonomicnervous system functioning (decreased sympathetic drive and parasympatheticascendance) because this may also have a beneficial effect on muscle toneby means of influencing muscle spindle activity (Banks, Jacobs, Gevirtz,& Hubbard, 1998). Training for balanced autonomic system functioning is facilitated by diaphragmatic breathing at a rate of about six breathsper  minute. Diaphragmatic breathing results in respiration and heartrate variability, presented as a line graph, following the same sinusoidalpattern when viewed on a biofeedback screen, a pattern termed respiratorysinus arrhythmia (RSA, Budzynski, 1989). This dual training of neurofeedbackto enhance SMR activity and RSA biofeedback for relaxed autonomic nervoussystem (ANS) functioning was done for 30 sessions over a six-month period.Results: Training was associated with significant reduction in dystonic movements. Additionally, the client became able to use diaphragmatic breathing tocue herself to turn on a mental state associated with increased SMR productionand thus control incidents of freezing, a common problem in advanced Parkinson's disease. With twelve more sessions over the next 18 months, the improved quality of life has been maintained. Discussion: This work is reported to put forth a theoretical model of why neurofeedback plus biofeedback is helpful in movement disorders and to encourage research in this area. 

Katzenschlager R, Lees AJ.  Olfaction and Parkinson's syndromes: its role in differential diagnosis. Curr Opin Neurol. 2004 Aug;17(4):417-23.
The National Hospital for Neurology and Neurosurgery, Queen Square, London, UK.
PURPOSE OF REVIEW: Marked olfactory dysfunction (hyposmia) is a frequent and early abnormality in Parkinson's disease. We review recent advances related to its cause and its clinical relevance with respect to the differential diagnosis of Parkinsonian syndromes. RECENT FINDINGS: Marked olfactory dysfunction occurs in Parkinson's disease and dementia with Lewy bodies but is not found in progressive supranuclear palsy and corticobasal degeneration. In multiple system atrophy, the deficit is mild and indistinguishablefrom cerebellar syndromes of other aetiologies, including the spino-cerebellar ataxias. This is in keeping with evidence of cerebellar involvement in olfactory processing, which may also help to explain recent findings of mild olfactory dysfunction in essential tremor. Smell testing remains, however, a clinically relevant tool in the differential diagnosis of indeterminate tremors. Intact olfaction has also been reported recently in Parkinson'sdisease (PARK 2) and vascular Parkinsonism. The relevance of sniffingability tool faction and a possible role of increased tyrosine hydroxylase and dopamine parts of the olfactory bulb are issues of current interestwith  respect to the physiology. The early or 'pre clinical' detectionof Parkinson's disease is increasingly recognized as an area in which olfactorytesting may be of value. SUMMARY: Research findings have confirmed a rolefor olfactory testing in the differential diagnosis of movement disorders, and suggest that this approach is currently under used in clinical practice.Validated test batteries are now available that may prove to be of practicaluse in the differential diagnosis of Parkinsonian syndromes and indeterminate tremors.

Zhang QJ, Zhang YY, Huang WY. [Traditional Chinese medicine in treatment of Parkinson's disease] [Article in Chinese] Zhong Xi Yi Jie He Xue Bao. 2004 Jan;2(1):75-7.
Institute of Cardio-cerebrovascular Disease, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China.
Parkinson's disease is a commonly encountered central nervous retrograde affection in elder persons. According to the theories of traditional Chinese medicine, Parkinson's disease is characterized by deficiency in the Ben (root) and excess in the Biao (branch). The Ben (root) is insufficiency of liver and kidney and deficiency of qi and blood; and the Biao (branch) is wind, fire, phlegm and stasis. Good therapeutic effects have been obtained by treatment based on syndrome differentiation, treatment with specific prescriptions and acupuncture. The further study on literature's, standardized criterion of symptoms differentiation and therapeutic effect determination as well as the screening and further research on the effective prescriptions and herbs should be paid more attention, meanwhile, the integration of herbs and acupuncture will be conducive to raise the therapeutic effect.

Xue, Y.; The Treatment of Parkinson's Disease By Acupuncture and Herbal Medicine The Journal of Chinese Medicine. 2003 Oct ; 73
ABSTRACT: This article discusses the aetiology and pathology of Parkinson's disease, its pattern identification according to Chinese medicine, and its treatment by body acupuncture, scalp acupuncture, pricking to bleed and Chinese herbal medicine.

Panikar, D.; Kishore, A.; Deep brain stimulation for Parkinson's disease Neurology India. 2003 Apr ; 51(2): 167-75
ABSTRACT: Dopaminerigic replacement therapy with levodopa/carbidopais still the cornerstone for the treatment of Parkinson's disease (PD).However, the medical management of PD is complicated by the appearanceof disabling motor response fluctuations, levodopa-induced dyskinesiasand psychosis. Since the early 1990s, surgical therapies have made a rapidreentry into the therapeutic armamentarium for PD and deep brain stimulation(DBS) of the globus pallidus interna or subthalamic nuclei is currentlythe most promising of such interventions. Recognition of the physiologicalchanges in basal ganglia circuits in animal models of PD has providedthe much needed theoretic basis for targeting these areas. DBS of theseareas has proven to be a safe procedure and effective against all themajor motor symptoms of PD. Though not curative it can substantially reducemotor response fluctuations, levodopa-induced dyskinesias, and improve the quality of life of these patients. DBS is an expensive treatment andhardware related complications are not rare. The results of the procedureare dependent on careful patient selection and the experience of the performingteam.  An update on the principles, methods and results of such proceduresis  essential to raise the awareness of this new therapeutic modalityand to provide guidelines to the referring physicians.

Hernandez-Reif, M.; Field, T.; Largie, S.; Cullen, C.; Beutler, J.; Sanders, C.; Weiner, W.; Rodriguez-Bateman, D.; Zelaya, L.; Schanber, S.;Kuhn,C.; Parkinson's disease symptoms are differentially affected by massagetherapy vs. progressive muscle relaxation: a pilot study Journalof Bodywork and Movement Therapies. 2002 Jul; 6(3): 177-82
ABSTRACT: Sixteen adults diagnosed with idiopathic Parkinson's disease (M age=58) received 30-min massage therapy or progressive muscle relaxation exercise sessions twice a week for 5 weeks (10 sessions total). Physicians rated participants in the massage therapy group as improved in daily living activities by the end of the study. The massaged group also rated themselves as improved in daily functioning, and having more effective and less disturbed sleep. Urine samples revealed that at the end of the 10 sessions, themassage therapy group had lower norepinephrine and epinephrine (stresshormone) levels, suggesting they were less stressed. The progressive musclerelaxation group had higher dopamine levels, which is interesting in thatParkinson's is associated with a decrease in dopamine. The relaxationgroup also showed higher epinephrine levels, suggesting that althoughthe relaxation exercises might have been beneficial, some Parkinson's participants might have found the relaxation technique stressful.

Duval, C.; Lafontaine, D.; Hebert, J.; Leroux, A.; Panisset, M.; Boucher, J.P.; The Effect of Trager Therapy on the Level of Evoked Stretch Responses in Patients with Parkinson's Disease and Rigidity Journal of Manipulative and Physiological Therapeutics. 2002 Sep; 25(7): 455-64
ABSTRACT: OBJECTIVE: To quantify changes of evoked stretch responses(ESR) in the most rigid arm of patients with Parkinson's disease (PD)after Trager therapy. METHODS: Gentle rocking motion associated with thistype of manual therapy was imparted to the upper limbs and body of 30patients for 20 minutes. A pretest and 2 posttests (at 1 and 11 minutesafter the treatment, respectively) were performed, consisting of electromyographic(EMG) recordings of the flexor carpi radialis and extensor digitorum communiswhile the patient's wrist was passively flexed and extended with an amplitudeof 60 degrees and a frequency of 1 Hz. Patients received the treatmenton the most rigid side of their bodies (ipsi-group) or on the contralateral side (contra-group). Half of patients in each group received the treatment while lying supine on a massage table (ipsi- and contra-supine) or sitting in a chair (ipsi- and contra-sitting). RESULTS: In general, the level of ESR reduced by 36% immediately after treatment and remained 32% lower than pretest values 11 minutes after treatment (F = 41.45, P <.05). Patients who received the treatment lying supine benefited from a 42% reductionof ESR (F = 4.07, P <.05). The side on which the treatment was performeddid not significantly influence the outcome of the treatment (F = 0.50,P>.05). However, post hoc analysis of the triple interaction (test sidex position) indicated that the sitting position was much less efficientfor sustained contralateral effect (P >.05). CONCLUSIONS: Results fromthe present study strongly suggest that it is possible to modify the levelof ESR by using Trager therapy. This stretch reflex inhibition may inducea reduction of the muscle rigidity seen in these patients. The presentresultsmay eventually lead to the development of a specific complementary therapy for patients with Parkinson's disease and rigidity.

Elster, EL.;  Upper Cervical Chiropractic Management of a Patient with Parkinson's Disease: A Case Report    Journalof Manipulative and Physiological Therapeutics. 2000 Oct; 23(8): 573-7
 ABSTRACT: Objective: To discuss the use of upper cervical chiropractic management in managing a single patient with Parkinson's disease and to describe the clinical picture of the disease.   Clinical Features: A 60-year-old man was diagnosed with Parkinson's disease at age 53 after a twitch developed in his left fifth finger. He later developed rigidity in his left leg, body tremor, slurring of speech, and memory loss among other findings.  Intervention and Outcome: This subject was managed with upper cervical chiropractic care for 9 months. Analysis of precision upper cervical radiographs determined upper cervical misalignment. Neurophysiology was monitored with paraspinal digital infrared imaging. This patient was placed on a specially designed knee-chest table for adjustment, which was delivered by hand to the first cervical vertebrae, according to radiographic findings. Evaluation of Parkinson's symptoms occurred by doctor's observation, the patient's subjective description of symptoms, and use of the Unified Parkinson's Disease Rating Scale. Reevaluations demonstrated a marked improvement in both subject and objective findings.  Conclusion: Upper cervical chiropractic care aided by cervical radiographs and thermal imaging had a successful outcome for a patient with Parkinson's disease. Further investigation into upper cervical injury has a contributing factor to Parkinson's disease should be considered.

Elster EL, Eighty-One Patients with Multiple Sclerosis and Parkinson's Disease Undergoing Upper Cervical Chiropractic Care to Correct VertebralSubluxation: A Retrospective Analysis, Journal of Vertebral Subluxation Research, August 2, 2004, pp 1-9 [http://www.jvsr.com/abstracts/index.asp?id=205]
Objective: The objective of this article is threefold: to examine the role of head and neck trauma as a contributing factor to the onset of Multiple Sclerosis (MS) and Parkinson's disease (PD); to explore the diagnosis and treatment of trauma-induced injury to the upper cervical spine through the use of protocol developed by the International Upper Cervical Chiropractic Association (IUCCA); and to investigate the potential for improving and arresting MS and PD through the correction of traumainduced upper cervical injury. Datafrom 81 MS and PD patients who recalled prior trauma, presented with uppercervical injuries, and received care according to the above protocol are
reviewed.  Clinical Features: Each patient was examined and caredfor in the author's private practice in an uncontrolled, non-randomized environment over a five-year period. Of the 81 MS and PD patients, 78 recalled that they had experienced at least one head or neck trauma prior to the onset of the disease. In order of frequency, patients reported that they were involved in auto accidents (39 patients); sporting accidents, such as skiing, horseback riding, cycling, and football (29 patients); or falls on icy sidewalks or down stairs (16 patients). The duration between the traumatic event and disease onset varied from two months to 30 years.  Intervention and Outcome: Two diagnostic tests, paraspinal digital infrared imaging and laser-aligned radiography, were performed according to IUCCA protocol. These tests objectively identify trauma-induced upper cervical subluxations (misalignment of theupper cervical spine from the neural canal) and resulting neuropathophysiology. Upper cervical subluxations were found in all 81 cases. After administering treatment to correct their upper cervical injuries, 40 of 44 (91%) MS cases and 34 of 37 (92%) PD cases showed symptomatic improvement and no further disease progression during the care period.   Conclusion: A causal link between trauma-induced upper cervical injury and disease onset for both MS and PD appears to exist. Correcting the injury to the upper cervical spine through the use of IUCCA protocol may arrest and reverse the progressionof both MS and PD. Further study in a controlled, experimental environmentwith a larger sample size is recommended.

Wells, MR.; Mc Carty, CL.; Smutny III, C.J.; Scandalis, TA.; Dittrich, F.; Fazzini, EA.; Fazzini, DO.; Osteopathic Manipulation in the Management of Parkinson's Disease: Preliminary Findings JAOA. 2000 Aug; 100(8): 521
ABSTRACT: Osteopathic manipulation has been shown to acutely improvethe gait function of patients with Parkinson disease. It is not clearif the acute effects of treatment will be improved or maintained withcontinued treatment. Hypothesis: Treatment with osteopathic manipulationwill produce functional improvements in the gait patients with Parkinson'sdisease if applied over a period of two months. The improvements resultingtreatment will slowly extinguish if treatment is discontinued. Methods:Patients with a prior diagnosis of idiopathic Parkinson's disease (n=15)and capable of ambulating unassisted off medication (Modified Hoehn andYahr stage II-III) and normal controls received an 8 week course of a defined osteopathic manipulation treatment regimen or a sham treatment.Quantitative gait parameters were monitored using a Peak Performance Technologies3-dimensional gait analysis system at time periods before the start oftreatment, at the end of treatment and 8 weeks after treatment was discontinued.Results: Preliminary results indicate that gait parameters including velocity,range of motion of joints and angular velocity improved in treated Parkinson'spatients and to some extent in treated normal controls, but not in shamtreated Parkinson's patients. The beneficial effects of treatment haddiminished, but were still detectable at two months after treatment. Conclusion:Preliminary results suggest a clear functional benefit of osteopathicmanipulation in Parkinson's patients treated over an 8 week period. Somebeneficial effects of treatment appear to persist even after treatmentis discontinued.

Wells, MR.; Giantinoto, S.; D'Agate, D.; Areman, RD.; Fazzini, EA.; Dowling, D.; Bosak, A.; Standard Osteopathic Manipulative Treatment Acutely Improves Gait Performance in Patients With Parkinson's Disease The Journal of the American Osteopathic Association. 1999 Feb; 99(2): 92-8
ABSTRACT: Patients with Parkinson's disease exhibit a variety of motor deficits which can ultimately result in complete disability. The primary objective of this study was to quantitatively evaluate the effect of osteopathic manipulative treatment (OMT) on the gait of patients with Parkinson'sdisease. Ten patients with idiopathic Parkinson's disease and a groupof eight age-matched normal control subjects were subjected to an analysis of gait before and after a single session of an OMT protocol. A separategroup of 10 patients with Parkinson's disease was given a sham-controlprocedure and tested in the same manner. In the treated group of patients with Parkinson's disease, statistically significant increases were observed in stride length, cadence, and the maximum velocities of upper and lower extremities after treatment. There were no significant differences observed in the control groups. The data demonstrate that a single session of an OMT protocol has an immediate impact on Parkinsonian gait. Osteopathic manipulation may be an effective physical treatment method in the management of movement deficits in patients with Parkinson's disease.

D'Agate, D.; Areman, RD.; Fazzini, EA.; Giantinoto, S.; Wells, M.; Bosak,A.;Osteopathic Manipulative Treatment Improves Functional Gait Performancein Patients With Parkinson's Disease The Journal of the AmericanOsteopathic Association. 1997 Aug; 97(8): 485
ABSTRACT: The primary objective of this study is to quantitatively evaluate osteopathic manipulative treatment on the functional activity of Parkinson's patients. Parkinson's patients experience varying degrees of bradykinesia, limb rigidity, and postural instability that causes the classic Parkinson's gait. Ten patients with idiopathic Parkinson's disease and ten normal, age-matched controls were subjected to an objective biomechanical analysis of their gait prior to and immediately after a single session of osteopathic manipulative treatment. Quantified parameters of gait were compared within subjects before and after the single session. The biomechanical analysis was performed using a computerized 2-dimensional sagittal gait analysis (Peak Technologies Inc.). Patients were off their Parkinson's medications for 12 hours prior to treatment and testing. The osteopathic treatment consisted of 14 primary muscle energy and articulatory techniques applied to the joints and musculature of the upper and lower limbs, trunk andspinal column. Statistically significant increase were observed in stridelength (p<0.021), cadence (p<0.018), and the maximum velocitiesof upper and lower extremities (p<0.05 criteria). In the control group of normal subjects, no statistically significant differences or trends in the various parameters of gait were evident compared to the pretreatment values. The preliminary data strongly indicate that a significant improvement in function is seen in Parkinson's patients after a single session ofosteopathic manipulative treatment.

Boehm KM, Lawner BJ, McFee RB. Study raises important issues about the potential benefit of osteopathy in the cranial field to patients with Parkinson's disease. J Am Osteopath Assoc. 2003 Aug;103(8):354-5; author reply 355-6. Free Full Text pdf

Rivera-Martinez S, Wells M, Capobianco J. A retrospective study of cranial strain patterns in patients with idiopathic Parkinson’s disease. Journal of the American Osteopathic Association. Aug 2002;102(8):417-422.  Free Full Text pdf
While providing osteopathic manipulative treatment to patients with Parkinson's disease at the clinic of the New York College of Osteopathic Medicine of New York Institute of Technology, physicians noted that these patients may exhibit particular cranial findings as a result of the disease. The purpose of this study was to compare the recorded observations of cranial strain patterns of patients with Parkinson's disease for the detection of common cranial findings. Records of cranial strain patterns from physician-recorded observations of 30 patients with idiopathic Parkinson's disease and 20 age-matched normal controls were compiled. This information was used to determine whether different physicians observed particular strain patterns in greater frequency between Parkinson's patients and controls. Patients with Parkinson's disease had a significantly higher frequency of bilateral occipitoatlantal compression (87% vs. 50%; P < .02) and bilateral occipitomastoid compression (40% vs. 10%; P < .05) compared with normal controls. Over subsequent visits and treatments, the frequency of both strain patterns were reduced significantly (occipitoatlantal compression, P < .01; occipitomastoid compression, P < .05) to levels found in the control group.

Rivera-Martinez S, Wells MR, Capobianco JD. Cranial Strain Patterns in Parkinson's Disease. JAOA. 2000 Aug; 100(8): 512
ABSTRACT: In the course of providing osteopathic treatment to patients with Parkinson's disease at the clinic of the New York College of Osteopathic Medicine, physicians noted that patients with this disease might exhibit particular cranial findings manifestly as a result of the disease. The purpose of this study was to compare the recorded observations of cranial strain patterns of Parkinson's patient treated by different physicians for the detection of common cranial findings. Records of cranial strain patterns from physician recorded observations of 30 patients with idiopathic Parkinson's disease and 20 age-matched normal controls were compiled.This information was used to determine if different physicians observedparticular strain patterns in greater frequency between Parkinson's patientsand controls. Parkinson's patients had a significantly higher frequencyof bilateral occipitoatlantal (OA) compression (87% vs. 50%; p<0.02)and bilateral occipitomastoid (OM) compression (40% vs. 10%; p<0.05) compared to normal controls. Over subsequent visits and treatments, the frequency of both strain patterns were reduced significantly (OA compression p<0.01; OM compression p<0.05) back to statistically normal levels of occurrence. The data suggests that there are cranial findings that may be expectedto occur at significantly greater frequency in patients with idiopathicParkinson's disease and that recurrence can be reduced with treatment.

Flanagan M.  Craniocervical Syndrome: Its Potential Role in Alzheimer's, Parkinson's and Other Diseases of the Brain.  Dynamic Chiropractic. 2001  Nov; 19(23). Free Full Text
Part I: Cranial Hydrodynamics and the Sutures The human brain has two drainage routes: one is through the transverse/sigmoid sinus system and into the internal jugular veins; the other is through the occipital marginal sinus system and into the vertebral venous plexus (VVP) inside the spinal canal. The internal jugular veins primarily drain the brain in the recumbent position. The VVP on the other hand is preferentially used to drain the brain in the upright position. Some authors refer to this system as the accessory drainage system. This article covers four parts: 1) sutures of the neurocranium and the role of the craniosacral primary respiratory rhythm (CSPR) in cranial hydrodynamics; 2) upright posture and the accessory drainage system and their role in cranial hydrodynamics; 3) how less effective designs, aging and injury of the craniocervical spine and accessory drainage system can lead to cranial hydrodynamic failure and chronic NPH; 4) how chronic NPH can lead to the type of pathology seen in Alzheimer's disease.

Flanagan M. Chronic NPH and Degenerative Brain Disease. Dynamic Chiropractic. 2002  Mar; 20(7).  Free Full Text
In the first part of this series, we discussed the role of the craniosacral primary respiratory rhythm in cranial hydrodynamics. In the second article, we discussed the role of the accessory drainage system (vertebral venous plexus,VVP) in humans and cranial hydrodynamics during upright posture. In the third article, we discussed the role of the craniocervicxal spine as the critical link between the cranial dural sinuses and the accessory drainage system, and how craniocervical syndromes may cause blockage or hydrodynamic failure of the cranial dural sinuses and subsequent chronic normal pressure hydrocephalus (NPH). In this last article, we will discuss a possible link between chronic NPH and Alzheimer's (AD), Parkinson's (PD) and other diseases.

Stanley, RK.; Protas, EJ.; Jankovic, J.; Exercise Performance in Those Having Parkinson's Disease and Healthy Normals Medicine & Science in Sports & Exercise. 1999 Jun; 31(6): 761-6
ABSTRACT: Objective: This study assessed and compared the cardiopulmonary function of individuals with Parkinson's disease (PD) with that of healthy normals in order to provide health professionals with more thorough information about the problems associated with PD. Methods: 20 men and 23 women were recruited from the Houston metropolitan area. Maximal oxygen consumption and time to maximal exercise in minutes were measured. Exercise was performed on a stationary bicycle using an incremental exercise protocol. Because the assumption of homogeneity of variance was not met for the dependent variable in women, the nonparametric Wilcoxon-Mann-Whitney-U analysiswas used . All other group comparisons were analyzed using an independent t-test.  Results: For men and women, there were no significant differences in Vo2max between those having PD and the HN. Likewise, there were no significantdifferencesin time max between women. Comparison of time max betweenmen did showa significant difference. Conclusions: Although there wereno significantdifferences in Vo2 max, indicating that individuals withPD may be lessefficient during exercise and therefore unable to exercise as long beforereaching Vo2 max. Although women with PD had a higher VO2max comparisonsof VO2 max and time max between those with PD and HN resultedin no significantdifferences.

Miyai, I.; Fujimoto, Y.; Ueda, Y.; Yamamoto, H.; Nozaki, S.; Saito, T.; Kang, J.; Treadmill training with body weight support: its effect on Parkinson's disease Archives of Physical Medicine and Rehabilitation. 2000 Jul; 81(7): 849-52
ABSTRACT: OBJECTIVE: To test whether body weight-supported treadmilltraining (BWSTT) is effective in improving functional outcome of patientswith Parkinson's disease. DESIGN: Prospective crossover trial. Patientswere randomized toreceive either a 4-week program of BWSTT with up to20% of their body weightsupported followed by 4 weeks of conventionalphysical therapy (PT), orthe same treatments in the opposite order. Medications for parkinsonism were not modified throughout the study. SETTING: Inpatient rehabilitation unit for neurologic diseases. SUBJECTS: Ten patients (5 men, 5 women) withHoehn and Yahr stage 2.5 or 3 parkinsonism; mean age 67.6 years, meanduration of Parkinson's disease 4.2 years. MAIN OUTCOME MEASURES: The UnifiedParkinson's Disease Rating Scale (UPDRS), ambulation endurance and speed(sec/10 m), and number of steps for 10-meter walk. RESULTS: The mean totalUPDRS before/after BWSTT was 31.6/25.6, and before/after PT was 29.1/28.0. Analysis of covariance for improvement of UPDRS demonstrated a significanteffect of type of therapy (F(1, 16) = 42.779, p < .0001) but not orderof therapy (F(1, 16) = 0.157, p = .697 1). Patients also had significantlygreater improvement with BWSTT than with PT in ambulation speed (BWSTT,before/after = 10.0/8.3; PT, 9.5/8.9), and number of steps (BWSTT, 22.3/19.6;PT, 21.5/20.8). CONCLUSIONS: In persons with Parkinson's disease, treadmilltraining with body weight support produces greater improvementin activitiesof daily living, motor performance, and ambulation thandoes physical therapy.

Levine, S.; Brandenberg, P.; Pagels, M.; Neuromuscular A Strenuous Exercise Program Benefits Patients with Mild to Moderate Parkinson's Disease Clinical Exercise Physiology. 2000 Feb ; 2(1): 43-8
ABSTRACT: Purpose: The purpose of this study was to determine the effectiveness of a strenuous exercise program on cardiovascular fitness and self-perceived ratings of symptoms that affect quality of life in patients with Parkinson's disease. Methods: Ten patients with mild to moderate Parkinson's disease participated in a 12-week exercise program consisting of cardiovascular, strength, flexibility, and balance exercises. An strand-Rhyming cycle ergometer test was performed prior to and at the completion of the program. Also, a self-perception questionnaire on Parkinson's symptoms affecting quality of life was completed at program completion. Statistical significance of cardiovascular fitness was analyzed using Student's paired t-test. Questionnaire results were reported as descriptive statistics. Results: Eight subjects completed the post-fitness evaluation and questionnaire. Cardiovascular fitness (i.e., estimated VáO2max) significantly (p < 0.01) improved (19.6 mL á kg_1 á min_1 to 24.3 mL á kg_1 á min_1), on the average, by 24%. Subjective impressions from the questionnaire revealed a unanimous improvement on Parkinson's symptoms that affect quality of life. Trouble with walking and feelings of well-being reported a 100% improvement, while shuffling during walking, leg strength, posture, rigidity, and trouble getting up from a chair reported at least a 75% improvement. Conclusions: For adults with mild to moderate Parkinson's disease, participation in and completion of a strenuous exercise program is feasible. Additionally, patients can experience benefits that will help alleviate symptoms affecting quality of life.

Rubinstein TC, Giladi N, Hausdorff JM. The power of cueing to circumvent dopamine deficits: a review of physical therapy treatment of gait disturbances in Parkinson's disease. Mov Disord. 2002 Nov;17(6):1148-60.
Movement Disorders Unit, Neurology Department, Tel-Aviv Sourasky Medical Center, and Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
Gait disturbances are among the primary symptoms of Parkinson's disease (PD) and contribute significantly to a patient's loss of function and independence. Standard treatment includes antiparkinsonian drugs, primarily levodopa. In addition to the standard drug regime, physical therapy is often prescribed to help manage the disease. In recent years, there have been promising reports of physical therapy programs combined with various types of sensory cueing for PD. In this brief review of the literature, we summarize the evidence regarding the clinical efficacy of different physical therapy programs for PD, specifically with respect to improving gait. We also discuss the potential therapeutic mechanisms of sensory cueing and review the studies that have used cueing in the treatment of gait in PD. This review of the literature shows two key findings: (1) despite its relatively long history, the evidence supporting the efficacy of conventional physical therapy for treatment of gait in PD is not strong; and (2) although further investigation is needed, sensory cueing appears to be a powerful means of improving gait in PD. Copyright 2002 Movement Disorder Society

Ma, H-I.; Trombly, C.A.; Tickle-Degnen, L.; Wagenaar, R.C.; Effect of One Single Auditory Cue on Movement Kinematics in Patients with Parkinson's Disease. American Journal of Physical Medicine. 2004 Jul; 83(7): 530-6
ABSTRACT: Objective: The purpose of this study was to determine whether one single auditory cue affected movement kinematics of more than one step in a sequential upper limb task in patients with Parkinson's disease. Design: A counter-balanced repeated-measures design was employed. A total of 16 male patients with Parkinson's disease and 16 age-matched male and female controls performed the task under two conditions. In the signal-present condition, the participants were instructed to start the movement when they heard a bell ring. In the signal-absent condition, there was no bell ringing, and they were told to start the movement when they were ready. Kinematic performances for the first two movement segments (i.e., reaching for the pen and bringing the pen to the paper) were compared between conditions. Results: The results indicated that the presence of the single auditory cue affected movement kinematics of the patients with Parkinson's disease but not that of the controls. When given external cueing, the patients elicited faster, more forceful, more efficient, more stable, but less smooth movement. Conclusions: The results suggest that therapists should provide external cues according to their treatment goals. In addition, researchers should be aware of the influence of start signals when designing subsequent experiments.

Bergen, J.L.; Toole, T.; Elliott III, R.G.; Wallace, B.; Robinson, K.; Maitland, C.G.; Aerobic exercise intervention improves aerobic capacity and movement initiation in Parkinson's disease patients Neurorehabilitation. 2002; 17(2): 161-8
ABSTRACT: Parkinson's Disease (PD) is a progressive neurologic disorder, which includes an inability to activate appropriate muscle activity. Very little research has analyzed aerobic exercise for PD patients. The purpose of this study was to investigate the effect of a 16 week aerobic exercise intervention on aerobic capacity and movement initiation (MI) time for PD patients. With 8 PD subjects (Hoehn & Yahr stage 2), 4 completed the exercise intervention. Peak VO_2scores significantly improved (26%) Choice MI improved from 532 ms to 415 ms, while simple MI improved from 285 ms to 261 ms. The improvement in aerobic capacity suggests that PD patients may benefit from exercise just as much as a normal population. The change in MI indicates that aerobic exercise may reduce the detrimental effects of neuromuscular slowing within PD patients, by improving the subjects' ability to initiate and perform appropriate movement patterns.

Freedland, R.L.; Festa, C.; Sealy, M.; Mcbean, A.; Elghazaly, P.; Capan, A.; Brozycki, L.; Nelson, A.J.; Rothman, J.; The effects of pulsed auditory stimulation on various gait measurements in persons with Parkinson's Disease Neurorehabilitation. 2002 ; 17(1) : 81-7
ABSTRACT: The purpose of this study was to examine the Functional Ambulation Performance Score (FAP; a quantitative gait measure) in persons with Parkinson's Disease (PD) using the auditory stimulation of a metronome (ASM). Participants (n = 16; 5F/11M; range 60--84 yrs.) had a primary diagnosis of PD and were all independent ambulators. Footfall data were collected while participants walked multiple times on an electronic walkway under the following conditions: 1) PRETEST: establishing baseline cadence, 2) ASM: metronome set to baseline cadence, 3) 10ASM: metronome set to 10% FAP scores increased between PRETEST and POSTTEST. PRE/POSTTEST comparisons also indicated decreases in cycle time and double support and increases in step length and step-extremity ratio (step length/leg length). The results confirm prior findings that auditory stimulation can be used to positively influence the gait of persons with PD and suggest beneficial effects of ASM as an adjunct to dopaminergic therapy to treat gait dysfunctions in PD.

Miyai, I.; Fujimoto, Y.; Yamamoto, H.; Ueda, Y.; Saito, T.; Nozaki, S.; Kang, J.; Long-term effect of body weight-supported treadmill training in Parkinson's disease: a randomized controlled trial Archives of Physical Medicine and Rehabilitation. 2002 Oct ; 83(10): 1370-3
ABSTRACT: OBJECTIVE: To investigate whether body weight-supported treadmill training (BWSTT) is of long-term benefit for patients with Parkinson's disease (PD). DESIGN: Randomized controlled trial. SETTING: Inpatient rehabilitation unit for neurologic diseases in Japan. PARTICIPANTS: Twenty-four patients (Hoehn and Yahr stages 2.5 or 3) who were not demented (Mini-Mental State Examination score, >27). INTERVENTIONS: Patients were randomized to receive either a 45-minute session of BWSTT (up to 20% of body weight supported) or conventional physical therapy (PT) for 3 days a week for 1 month. MAIN OUTCOME MEASURES: Outcome measures were evaluated at baseline and at 1, 2, 3, and 6 months. Measures included the Unified Parkinson's Disease Rating Scale (UPDRS), ambulation speed (s/10 m), and number of steps taken for a 10-m walk as a parameter for stride length. RESULTS: Four patients needed modification of medications in the follow-up period. Twenty patients (BWSTT, n=11; PT, n=9) without modified medications were analyzed for functional outcome. Age, duration of PD, gender, and doses of medications were comparable. There was no difference in the baseline UPDRS (BWSTT=33.3; PT=32.6), speed (BWSTT=10.8; PT=11.5), and steps (BWSTT=23.4; PT=22.8). The BWSTT group had significantly greater improvement than the PT group (Mann-Whitney U test, Bonferroni adjustment for multiple comparison) in ambulation speed at 1 month (BWSTT=8.5; PT=10.8; P<.005); and in the number of steps at 1 (BWSTT=20.0; PT=22.7; P<.005), 2 (BWSTT=19.5; PT=22.4; P<.005), 3 (BWSTT=20.1; PT=23.1; P<.005), and 4 months (BWSTT=21.0; PT=23.0; P=.006). CONCLUSIONS: BWSTT has a lasting effect specifically on short-step gait in PD.

Reuter, I.; Engelhardt, M.; Exercise Training and Parkinson's Disease: Placebo or Essential Treatment? Physician and Sportsmedicine. 2002 Mar; 30(3): 43-50
ABSTRACT: Exercise training is often recommended for patients who have Parkinson's disease. Until the debate about the pathophysiologic cause of impaired movement in parkinsonism is settled, it is difficult to develop a specific exercise treatment for symptoms that include hypokinesia, tremor, and muscular rigidity. Most of the published studies show a benefit of exercise training, and we provide an overview of the most essential studies and present conclusions for a practical approach to exercise training in parkinsonism.

Scandalis, T.A.; Bosak, A.; Berliner, J.C.; Helman, L.L.; Wells, M.R.; Resistance Training and Gait Function in Patients with Parkinson's Disease American Journal of Physical Medicine & Rehabilitation. 2001 Jan; 80(1): 38-43 .
ABSTRACT: Objective: To determine whether patients with Parkinson's disease who are enrolled in a resistance training program can gain strength similar to that of normal control subjects and whether these gains in strength would improve their gait function.
Design: Subjects included 14 patients with mild-to-moderate Parkinson's disease of either gender and six normal control subjects of similar age. The training consisted of an 8-wk course of resistance training twice per week, focused primarily on the lower limbs. The primary outcome measures consisted of exercise performance monitoring and quantitative gait analysis before and after the training course.
Results: Both the patients with Parkinson's disease and normal control subjects significantly increased their performance with resistance training. Subjects with Parkinson's disease had gains in strength similar to those of normal elderly adults. Patients with Parkinson's disease also had significant gains in stride length, walking velocity, and postural angles compared with pretreatment values.
Conclusions: Patients with mild-to-moderate Parkinson's disease can obtain increases in performance or strength similar to that of normal adults of the same age in a resistance training program. Resistance training can produce functional improvements in gait and may, therefore, be useful as part of a physical rehabilitation and/or health maintenance program for patients with Parkinson's disease.

De Goede, C.; Keus, S.; Kwakkel, G.; Wagenaar, R.; The effects of physical therapy in Parkinson's disease: a research synthesis Archives of Physical Medicine and Rehabilitation. 2001 Apr; 82(4): 509-15
ABSTRACT: OBJECTIVE: To present a critical review and meta-analysis of studies evaluating the effects of physical therapy in patients suffering from Parkinson's disease (PD), in terms of neurologic signs, activities of daily living (ADLs), and walking ability. DATA SOURCES: Articles published from 1966 to May 1999 were compiled by means of MEDLINE, Cochrane register of controlled trials, and CINAHL using combinations of the key words Parkinson's disease, exercise, exercise therapy, physical therapy, and group training. References presented in relevant publications were also examined. Articles written in English, German, or Dutch were included. STUDY SELECTION: Studies had to meet the following selection criteria: (1) patients with PD were included in the intervention study, (2) the effects of physical therapy (PT) were evaluated, (3) the study could be classified as true or quasi-experiment, and (4) the study was published in a journal or book. DATA EXTRACTION: Two reviewers assessed independently the methodologic quality of the data of each included study. One reviewer extracted relevant meta-analysis data. DATA SYNTHESIS: For each outcome measure the estimated effect size and the summary effect size (SES) were calculated, using fixed (ie, Hedges's g) and random effects models. The meta-analysis resulted in a significant homogeneous SES with regard to ADLs (.40; confidence interval [CI] = .17-.64) and stride length (.46; CI = .12-.82). The SES with regard to walking speed showed a significant heterogeneous SES, which remained significant after applying a random effects model (.49; CI = .21-.77). The SES with regard to neurologic signs was not significant (.22; CI = -.08 to .52). The small number of studies included and the shortcomings of the methodologic quality of these studies, however, bias the results of the present study. CONCLUSIONS: The results of the present research synthesis support the hypothesis that Parkinson patients benefit from PT added to their standard medication. Zijlstra, W.; Rutgers, A. W. F.; Van Weerden, T. W.; Voluntary and involuntary adaptation of gait in Parkinson's disease Gait and Posture. 1998 Jan; 7(1): 53-63
ABSTRACT: Voluntary and involuntary adaptation of gait in Parkinson's disease (PD) were studied in two separate experiments. In the first experiment, effects of changes in voluntary control were studied by asking PD patients and age-matched healthy subjects to adapt their walking pattern to visual cues resulting in spatial constraints, and auditory cues resulting in temporal constraints on stepping movements. In the second experiment, the adaptation to increases in speed during overground and treadmill walking was studied. Most patients were able to adapt their walking patterns in accordance with instructions. Notwithstanding consistent differences in step length, the adaptation to different conditions under study was highly similar in PD patients and healthy subjects. Only during walking with visually guided step length were the observed adaptations in PD patients less consistent. Contrary to these dissimilarities, the involuntary adaptation of timing of support and swing phases within the stride cycle was very similar between groups. In all conditions, only with changes in step length could a change in relative timing be observed. Our findings show that voluntary adaptation of gait is possible in PD and that basic involuntary coordination mechanisms are preserved. The observed disturbances in stride length regulation probably reflect an inability to perform fast movements in PD.

Canning, C.; Alison, J.; Allen, N.; Groeller, H.; Parkinson's disease: an investigation of exercise capacity, respiratory function, and gait Archives of Physical Medicine and Rehabilitation. 1997 Feb; 78(2): 199-207
ABSTRACT: OBJECTIVE: To evaluate the exercise capacity of subjects with mild to moderate Parkinson's disease and determine whether abnormalities in respiratory function and gait affect exercise capacity. DESIGN: Descriptive. Subjects were categorized according to exercise history, disease severity, and presence/absence of upper airway obstruction. SUBJECTS AND SETTING: Sixteen volunteers with mild to moderate idiopathic Parkinson's disease attended a university research laboratory. MAIN OUTCOME MEASURES: Subjects performed a maximum exercise test on a cycle ergometer, together with respiratory function tests and a walking test. Peak values for oxygen consumption and work rate were recorded for the maximum exercise test. Measures of respiratory function included spirometry, flow-volume loops, lung volumes, and mouth pressures. Velocity, stride length, and cadence were measured for preferred and fast speeds of walking. The values obtained on each of these tests were compared with published predicted age- and gender-matched normal values. RESULTS: Peak oxygen consumptions and peak work loads achieved by subjects with Parkinson's disease were not significantly different from normal values, despite evidence of respiratory and gait abnormalities typical of Parkinson's disease. Exercise category was significantly correlated with percent predicted VO2peak (r = .64, p < .01), with sedentary subjects producing lower scores than exercising subjects. There was no significant correlation between disease severity and percent predicted VO2peak. CONCLUSION: Despite their neurological deficit, individuals with mild to moderate Parkinson's disease have the potential to maintain normal exercise capacity with regular aerobic exercise.

Leyton M, Dagher A, Boileau I, Casey K, Baker GB, Diksic M, Gunn R, Young SN, Benkelfat C. Decreasing amphetamine-induced dopamine release by acute phenylalanine/tyrosine depletion: A PET/[11C]raclopride study in healthy men. Neuropsychopharmacology. 2004 Feb;29(2):427-32.
Department of Psychiatry, McGill University, Montreal, Quebec, Canada. marco.leyton@mcgill.ca
Acute phenylalanine/tyrosine depletion (APTD) has been proposed as a new method to decrease catecholamine neurotransmission safely, rapidly, and transiently. Validation studies in animals are encouraging, but direct evidence in human brain is lacking. In the present study, we tested the hypothesis that APTD would reduce stimulated dopamine (DA) release, as assessed by positron emission tomography (PET) and changes in [(11)C]raclopride binding potential (BP), a measure of DA D2/D3 receptor availability. Eight healthy men received two PET scans, both following d-amphetamine, 0.3 mg/kg, p.o., an oral dose known to decrease [(11)C]raclopride BP in ventral striatum. On the morning before each scan, subjects ingested, in counter-balanced order, an amino-acid mixture deficient in the catecholamine precursors, phenylalanine, and tyrosine, or a nutritionally balanced mixture. Brain parametric images were generated by calculating [(11)C]raclopride BP at each voxel. BP values were extracted from the t-map (threshold: t=4.2, equivalent to p<0.05, Bonferroni corrected) and a priori identified regions of interest from each individual's coregistered magnetic resonance images. Both receptor parametric mapping and region of interest analyses indicated that [(11)C]raclopride binding was significantly different on the two test days in the ventral striatum (peak t=6.31; x=-25, y=-8, and z=0.1). In the t-map defined cluster, [(11)C]raclopride BP values were 11.8+/-11.9% higher during the APTD session (p<0.05). The reduction in d-amphetamine-induced DA release exhibited a linear association with the reduction in plasma tyrosine levels (r=-0.82, p<0.05). Together, the results provide the first direct evidence that APTD decreases stimulated DA release in human brain. APTD may be a suitable new tool for human neuropsychopharmacology research.

On 1/4/05 3:54 AM, "DrCBlum@aol.com" <DrCBlum@aol.com> wrote:
Dear Dr. Leyton,
I read the abstract of your article with great interest. I have a close friend and patient who has recently been diagnosed with Parkinson's. While treatment with Levodopa is likely in the future, the hope of delaying this therapy is a desirable alternative.
I have had a few patients who successfully treated their resting tremors with L Tyrosine supplementation. Do you think there is any reason to assume that a patient with early onset Parkinson's might benefit from L Tyrosine and or L Phenylalanine supplementation?
Any suggestions you might have to offer would be greatly appreciated.
Charles

Subj: Re: Tyrosine and Dopamine Production
Date: 1/4/2005 8:42:02 AM Eastern Standard Time
From: Marco Leyton <marco.leyton@mcgill.ca>
To: <DrCBlum@aol.com>

Dear Dr. Blum,
The administration of tyrosine supplements can increase dopamine release in the striatum in rats (eg, During et al 1988; Tam et al 1990), and the same effect could be expected in humans. There are also reports that tyrosine can improve coping with stressful situations (eg, Banderet and Lieberman, 1989) and facilitate abstinence in opiate- and alcohol-dependent patients (Chen et al. 2004). I am not aware, though, of any clinical trials testing the efficacy of tyrosine supplementation in Parkinson's Disease.
Beyond that, I wish your friend and patient the very best. Please note that I am neither a physician nor a neurologist, and so my comments above should be considered information rather than treatment advice. A neurologist, of course, would be best positioned to advise whether a brief trial of tyrosine supplements would be worth trying.
Best regards,
ML

Banderet LE, Lieberman HR (1989): Treatment with tyrosine, a neurotransmitter precursor, reduces environmental stress in humans. Brain Res Bull 22:759-762
Chen, T. J. H., Blum, K., Payte, J. T., Schoolfield, J., Hopper, D., Stanford, M., Braverman, E. R. (2004). Narcotic antagonists in drug dependence: pilot study showing enhancement of compliance with SYN-10, amino-acid precursors and enkephalinase inhibition therapy. Medical Hypotheses 63, 538-548
During MJ, Acworth IN, Wurtman RJ (1988): Effects of systemic L-tyrosine on dopamine release from rat corpus striatum and nucleus accumbens. Brain Res 452:378-380
Tam SY, Elsworth JD, Bradberry CW, Roth RH (1990): Mesocortical dopamine neurons: high basal firing frequency predicts tyrosine dependence of dopamine synthesis. J Neural Transm 81:97-110
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Marco Leyton, Ph.D.
Assistant Professor
Department of Psychiatry
Department of Neurology & Neurosurgery
McGill University
1033 Pine Avenue West
Montreal, Qc H3A 1A1

Montgomery AJ, McTavish SF, Cowen PJ, Grasby PM. Reduction of brain dopamine concentration with dietary tyrosine plus phenylalanine depletion: an [11C]raclopride PET study. Am J Psychiatry. 2003 Oct;160(10):1887-9.
Imperial College, School of Medicine, University Department of Psychiatry, Warneford Hospital, Oxford, UK.
OBJECTIVE: Extracellular dopamine concentrations were estimated through measurement of [(11)C]raclopride binding with positron emission tomography after dietary manipulation of the dopamine precursors tyrosine and phenylalanine. METHOD: Healthy male subjects were scanned on two occasions: once after receiving a balanced amino acid drink and once after receiving a drink mixture from which tyrosine and phenylalanine were omitted. RESULTS: Dietary tyrosine and phenylalanine depletion increased [(11)C]raclopride binding in the striatum by a mean of 6%. The change in [(11)C]raclopride binding correlated significantly with the fall in the ratio of tyrosine and phenylalanine to large neutral amino acids. CONCLUSIONS: This is the first demonstration of an effect of a dietary manipulation on brain dopamine release in humans. This result provides support for the further investigation of the role of dietary manipulations in the treatment of neuropsychiatric disorders.

Harmer CJ, McTavish SF, Clark L, Goodwin GM, Cowen PJ.Tyrosine depletion attenuates dopamine function in healthy volunteers. Psychopharmacology (Berl). 2001 Feb;154(1):105-11.
University Department of Psychiatry, Warneford Hospital, Oxford, UK. catherine.harmer@psych.ox.ac.uk
RATIONALE: Tyrosine depletion has been shown to reduce dopamine over activity in animal and human investigations. However, the effects on basal dopamine function have not been explored. Such information could establish tyrosine depletion as an effective probe of dopamine function in healthy volunteers and would also have relevance for future therapeutic applications of this manipulation. OBJECTIVE: The present study investigated the effect of acute tyrosine depletion on dopamine function in healthy volunteers using a combination of neuroendocrine, neuropsychological and subjective measures. METHODS: On one occasion, volunteers received an amino acid drink selectively lacking tyrosine and phenylalanine (TYR-free), whilst on the other they received a balanced (BAL) amino acid drink. Plasma prolactin, amino acid levels and subjective state were monitored over 6 h following the two drinks, and volunteers also completed a battery of tests from the CANTAB, including measures of spatial memory previously found to be sensitive to changes in dopamine function. RESULTS: Plasma prolactin levels rose following the TYR-free drink relative to the balanced mixture, indicative of decreased dopamine neurotransmission within the hypothalamus. Following the TYR-free drink, volunteers were impaired at spatial recognition memory and spatial working memory. Volunteers also tended to report that they felt less good following the TYR-free than the BAL mixture. CONCLUSION: Tyrosine depletion in healthy volunteers affected baseline dopamine function on the different measures employed in this study. Tyrosine depletion would thereby seem valuable as a probe of dopamine function in human volunteers. Ratings of depression and other aspects of cognitive function were unaffected, suggesting that this manipulation may be free of significant side effects when used as a treatment for conditions characterised by dopamine over activity, such as acute mania and schizophrenia.Tong ZY, Kingsbury AE, Foster OJ. Up-regulation of tyrosine hydroxylase mRNA in a sub-population of A10 dopamine neurons in Parkinson's disease. Brain Res Mol Brain Res. 2000 Jun 23;79(1-2):45-54.
Parkinson's Disease Society Brain Research Centre (Brain Bank), Institute of Neurology, London, UK.
Neuronal injury has been consistently found in A10 midbrain dopamine neurons in Parkinson's disease (PD). To assess changes in neurotransmitter-related gene transcription, in these neurons in PD, tyrosine hydroxylase (TH) mRNA expression was examined in the ventral tegmental area (VTA) of seven PD cases and seven control subjects, using in situ hybridization histochemistry (ISHH). In controls, TH mRNA expression was found in both melanised and non-melanised neurons in the VTA. Neither population expressed dopamine beta-hydroxylase (DBH). Of the melanised neurons, 99% were TH mRNA positive. The level of the TH mRNA signal (expressed as grain density per cell) was similar in the two populations (melanised: 0.129+/-0.004 (mean+/-S.E.M.), n=142 vs. non-melanised: 0.138+/-0.006, n=89, P>0.05, Student's t-Test). In PD cases there was no significant change in TH mRNA expression in melanised neurons (0.138+/-0.003, n=196), and the proportion of positively labeled melanised neurons was 98%. However, non-melanised neurons showed significantly higher TH mRNA (0.163+/-0.006, n=87) than non-melanised neurons in control subjects (P<0.005) and melanised neurons in the PD cases (P<0.0005). This up-regulation of TH mRNA expression in non-melanised neurons may suggest the existence of a compensatory mechanism at presynaptic level.

Vitreshchak TV, Poleshchuk VV, Piradov MA. [Plasma levels of mediator amino acids in patients with Parkinson disease] [Article in Russian] Biomed Khim. 2004 Jan-Feb;50(1):92-9.
Institute of Neurology, Russian Academy of Medical Sciences, Volokolamskoe Shosse 80, 125367 Moscow, Russia.
Content of neurotransmitter amino acids before and after treatment with He-Ne-laser was measured in blood of two groups of the Parkinson's disease patients distinguished by low (first group) and high (second group) activity of monoamine oxidase B and Cu/Zn-superoxide dismutase. An increase in taurine level at the early stage of the disease (first group of patients) suggests that taurine may be a marker of compensatory abilities of the organism. The violation of the glutamate/taurine balance at the later stages of the disease and its normalization following the laserotherapy accompanied improvement of neurological symptoms.Engelborghs S, Marescau B, De Deyn PP. Amino acids and biogenic amines in cerebrospinal fluid of patients with Parkinson's disease. Neurochem Res. 2003 Aug;28(8):1145-50.
Department of Neurology, Laboratory of Neurochemistry and Behavior, Born-Bunge Foundation, University of Antwerp, Belgium.
To study changes in amino acid metabolism and biogenic amines in Parkinson's disease, we set up a prospective study and measured biogenic amines, their main metabolites, and 22 different amino acids, in cerebrospinal fluid of Parkinson's disease patients (n = 24) and age-matched controls (n = 30). A trend toward higher dopamine levels in Parkinson's disease patients was interpreted as an effect of treatment with levodopa and/or selegiline. Significantly lower concentrations of the dopamine metabolite 3,4-dihydroxyphenylacetic acid in the Parkinson's disease group might reflect dopaminergic cell loss. Our results revealed decreased serotonin catabolism that was interpreted as an effect of treatment with selegiline. Whereas all amino acid levels were unchanged, taurine was significantly lower in Parkinson's disease patients. Studies showed that taurine exerts a trophic action on the central nervous system. In this view, decreased taurine in a neurodegenerative disorder as Parkinson's disease deserves attention.

Haglin L, Selander B. [Diet in Parkinson disease] [Article in Norwegian] Tidsskr Nor Laegeforen. 2000 Feb 20;120(5):576-8.
ocialmedicinska kliniken Norrlands Universitetssjukhus, Umea.
The interest in a protein redistribution diet, also called daytime protein restriction diet, has increased among patients with Parkinson's disease. Since certain amino acids compete with L-dopa in the intestine and at theblood-brain barrier, daytime protein restriction may improve fluctuations in motor ability. However, this diet can contribute to weight loss, nutrient deficiencies and cause cognitive disabilities if the diet is not correctly observed. Further studies are needed to clarify how medication with L-dopa in combination with different diets (relative contributions of protein, fat and carbohydrate) may affect motor fluctuations, nutritional status and cognitive ability.

Beal, M.F.; Shults, C.W.; Effects of Coenzyme Q_{10} in Huntington's disease and early Parkinson's disease Biofactors. 2003 18(1-4): 153-61
ABSTRACT: There is increasing interest in the potential usefulness of coenzyme Q10 (CoQ10) to treat both mitochondrial disorders as well as neurodegenerative diseases such as Parkinson's Disease (PD), Huntington's Disease (HD),and Amyotrophic Lateral Sclerosis (ALS). CoQ10 may also be useful in treatingFreidriech's Ataxia, which is caused by a mutation in the protein frataxinlocalized to mitochondria. In this paper we will focus on recent studiesinvolving CoQ10 and Huntington's Disease and Parkinson's Disease. CoQ10is composed of a quinone ring and a 10-isoprene unit tail and is distributedin all membranes throughout the cell. CoQ10 serves as an important co-factorof the electron transport chain where it accepts electrons from complexesI and II. It is initially reduced to the semi-ubiquinone radical and thentransfers electrons one at a time to complex III of the electron transport chain [1,2] CoQ10, which is also known as ubiquinone, serves as an improtant antioxidant in both mitochondria and lipid membranes. It mediates someof its antioxidant effects through interactions with alpha-tocopherol[1,3].

Shults CW. Coenzyme Q10 in neurodegenerative diseases. Curr Med Chem. 2003 Oct;10(19):1917-21.
Department of Neurosciences, University of California, San Diego, LaJolla, CA 92093-0662, USA. cshults@ucsd.edu
Coenzyme Q(10) (ubiquinone), which serves as the electron acceptor for complexes I and II of the mitochondrial electron transport chain and also acts as an antioxidant, has the potential to be a beneficial agent in neurodegenerativediseases in which there is impaired mitochondrial function and/or excessiveoxidative damage. Substantial data have accumulated to implicate theseprocesses in the pathogenesis in certain neurodegenerative disorders,including Parkinson's disease, Huntington's disease and Friedreich's ataxia.Although no study to date has unequivocally demonstrated that coenzymeQ(10) can slow the progression of a neurodegenerative disease, recentclinical trials in these three disorders suggest that supplemental coenzymeQ(10) can slow the functional decline in these disorders, particularly Parkinson's disease.

Ebadi, M.; Govitrapong, P.; Sharma, S.; Ubiquinone (Coenzyme q(10)) and Mitochondria in Oxidative Stress of Parkinson's Disease Biological Signals and Receptors. 2001; 10: 224-253
ABSTRACT: Parkinson's disease is the second most common neurodegenerative disorder after Alzheimer's disease affecting approximately1% of the population older than 50 years. There is a worldwide increase in disease prevalence due to the increasing age of human populations. A definitive neuropathological diagnosis of Parkinson's disease requires loss of dopaminergic neurons in the substantia nigra and related brain stem nuclei, and the presence of Lewy bodies in remaining nerve cells. The contribution of genetic factors to the pathogenesis of Parkinson's disease is increasingly being recognized. A point mutation which is sufficient to cause a rare autosomal dominant form of the disorder has been recently identified in the alpha-synuclein gene on chromosome 4 in the much more common sporadic, or 'idiopathic' form of Parkinson's disease, and a defect of complex I of the mitochondrial respiratory chain was confirmed at the biochemical level. Disease specificity of this defect has been demonstrated for the parkinsonian substantia nigra. These findings and the observation that the neurotoxin 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine (MPTP), which causes a Parkinson-like syndrome in humans, acts via inhibition of complex I have triggered research interest in the mitochondrial genetics of Parkinson's disease. Oxidative phosphorylation consists of five protein-lipid enzyme complexes located in the mitochondrial inner membrane that contain flavins (FMN, FAD), quinoid compounds (coenzyme Q10, CoQ10) and transition metal compounds (iron-sulfur clusters, hemes, protein-bound copper). These enzymes are designated complex I (NADH:ubiquinone oxidoreductase, EC 1.6. 5.3), complex II (succinate:ubiquinone oxidoreductase, EC 1.3.5.1), complex III (ubiquinol:ferrocytochrome c oxidoreductase, EC1.10.2.2), complex IV (ferrocytochrome c:oxygen oxidoreductase or cytochrome c oxidase, EC 1.9.3.1), and complex V (ATP synthase, EC 3.6.1.34). A defect in mitochondrial oxidative phosphorylation, in terms of a reduction in the activity of NADH CoQ reductase (complex I) has been reported in the striatum of patients with Parkinson's disease. The reduction in the activity of complex I is found in the substantia nigra, but not in other areas of thebrain, such as globus pallidus or cerebral cortex. Therefore, the specificityof mitochondrial impairment may play a role in the degeneration of nigrostriataldopaminergic neurons. This view is supported by the fact that MPTP generating1-methyl-4-phenylpyridine (MPP(+)) destroys dopaminergic neurons in thesubstantia nigra. Although the serum levels of CoQ10 is normal in patientswith Parkinson's disease, CoQ10 is able to attenuate the MPTP-inducedloss of striatal dopaminergic neurons.

Sudha, K.; Rao, A.V.; Rao, S.; Rao, A.; Free radical toxicity and antioxidants in Parkinson's disease Neurology India. . 2003 Jan; 51(1): 60-2
ABSTRACT: Erythrocyte lipid peroxidation, oxidative hemolysis, erythrocyte antioxidant enzymes, viz. superoxide dismutase, glutathione reductase, glutathione peroxidase, catalase and plasma antioxidants, viz. vitamin A, vitamin E, vitamin C and ceruloplasmin have been determined by spectrophotometric methods in 15 patients with Parkinson's disease (PD) and in 50 controls. Lipid peroxidation, oxidative hemolysis and plasma ceruloplasmin were significantlyhigher in PD patients as compared to normals. Erythrocyte antioxidantsin PD patients were not significantly different from the controls. However,plasma vitamin C in PD patients was significantly lower than the controls.It is concluded that these patients are under oxidative stress which pointsto a possible involvement of free radicals in PD.

Kaur D, Andersen JK. Ironing out Parkinson's disease: is therapeutic treatment with iron chelators a real possibility? Aging Cell. 2002 Oct;1(1):17-21.
Buck Institute for Age Research, 8001 Redwood Blvd, Novato, CA 94945, USA.
Levels of iron are increased in the brains of Parkinson's disease (PD) patients compared to age-matched controls. This has been postulated to contribute to progression of the disease via several mechanisms including exacerbation of oxidative stress, initiation of inflammatory responses and triggering of Lewy body formation. In this minireview, we examine theputative role of iron in PD and its pharmacological chelation as a prospectivetherapeutic for the disease.

Mcintosh, GC.; Holden, KE.; Risk for Malnutrition and Bone Fracture in Parkinson's Disease: A Pilot Study Journal Of Nutrition For TheElderly. 1999; 18(3): 21-31
ABSTRACT: Conditions relating to Parkinson's disease include tremor,impaired balance, falls, constipation, food-medication interactions, andanorexia. Weight loss, bone thinning and muscle wasting are common, raisingrisk for malnutrition and bone fracture. This pilot study examines thelifestyle and dietary choices of 24 Parkinson's patients. Unplanned weightloss and falls were common, and most had multiple risk factors for malnutrition and fracture. Results support findings in previous studies and call for early nutrition intervention to help prevent fractures, muscle wasting, bowel impaction, and dehydration. The findings indicate that such intervention could prevent hospitalizations and related costs.

Martinez, M.; Martinez, N.; Hernandez, AI.; Fernandiz, ML.; Hypothesis: Can N-Acetylcysteine be Beneficial in Parkinson's Disease? Life Sciences. 1999; 64: 1253-7
ABSTRACT: Based on the findings of decreased mitochondrial complex Iactivity in the substantia nigra of patients with Parkinson's disease,we propose that the consequent reduction of ATP synthesis and increasedgeneration of reactive oxygen species may be a possible cause of nigrostriatalcell death. Since sulfhydryl groups are essential in oxidative phosphorylation, thiolic antioxidants may contribute to the preservation of these proteins against oxidative damage. In the present paper, we hypothesize that treatment with a sulfur-containing antioxidant such as N-acetylcysteine may provide a new neuroprotective therapeutic strategy for Parkinson's disease.

Sechi, G.; Deledda, MG.; Bua, G.; Reduced Intravenous Glutathione in the Treatment of Early Parkinson's Disease Progress in Neuro-Psychopharmacology & Biological Psychiatry. 1996 Oct; 20(7): 1159-70
ABSTRACT: 1. Several studies have demonstrated a deficiency in reduced glutathione (GSH) in the nigra of patients with Parkinson's Disease (PD). In particular, the magnitude of reduction in GSH seems to parallel the severity of the disease. This finding may indicate a means by which the nigra cells could be therapeutically supported. 2. The authors studied the effects of GSH in nine patients with early, untreated PD. GSH was administeredintravenous, 600 mg twice daily, for 30 days, in an open label fashion.Then, the drug was discontinued and a follow-up examination carried-outat 1-month interval for 2-4 months. Thereafter, the patients were treatedwith carbidopa-levodopa. 3. The clinical disability was assessed by usingtwo different rating scale and the Webster Step-Second Test at baseline and at 1-month interval for 4-6 months. All patients improved significantly after GSH therapy, with a 42% decline in disability. Once GSH was stoppedthe therapeutic effect lasted for 2-4 months. 4. Our data indicate thatin untreated PD patients GSH has symptomatic efficacy and possibly retardsthe progression of the disease.

Haneishi, E.; Effects of a music therapy voice protocol on speech intelligibility, vocal acoustic measures, and mood of individuals with Parkinson's disease Journal of Music Therapy. 2001 Win; 38(4): 273-90
ABSTRACT: This study examined the effects of a Music Therapy Voice Protocol (MTVP) on speech intelligibility, vocal intensity, maximum vocal range, maximum duration of sustained vowel phonation, vocal fundamental frequency, vocal fundamental frequency variability, and mood of individuals with Parkinson's disease. Four female patients, who demonstrated voice and speech problems,served as their own controls and participated in baseline assessment (studypretest), a series of MTVP sessions involving vocal and singing exercises,and final evaluation (study posttest). In study pre and posttests, datafor speech intelligibility and all acoustic variables were collected.Statistically significant increases were found in speech intelligibility,as rated by caregivers, and in vocal intensity from study pretest to posttestas the results of paired samples t-tests. In addition, before and aftereach MTVP session (session pre and posttests), self-rated mood scoresand selected acoustic variables were collected. No significant differences were found in any of the variables from the session pretests to posttests,across the entire treatment period, or their interactions as the resultsof two-way ANOVAs with repeated measures. Although not significant, themean of mood scores in session posttests (M = 8.69) was higher than thatin session pretests (M = 7.93).

Stallibrass, C.; Hampson, M.; The Alexander technique: its application in midwifery and the results of preliminary research into Parkinson's Complementary Therapies In Nursing & Midwifery. 2001 Feb; 7(1): 13-8
ABSTRACT: This article outlines the origins and theory of the Alexander Technique and how it is learnt. Recent research is listed and a description given of main presenting symptoms and medical problems of pupils coming for lessons. The paper also describes how the Alexander Technique is used by women in pregnancy and childbirth and explains why it is beneficial. The final section describes Parkinson's research results, mainly from apreliminary study designed some years ago to test a methodology for arandomized controlled trial. Ramig, LO.; Treatment of Speech and Voice Problems Associated With Parkinson's Disease Topics In Geriatric Rehabilitation. 1998 Dec; 14(2): 28-43
ABSTRACT: Speech and voice problems occur in most individuals with idiopathic Parkinson's disease. While all aspects of speech production may be affected, disordered voice is one of the most common problems. Previous forms of treatment for the disorder of speech and voice in individuals with idiopathic Parkinson's disease have had modest effectiveness. The LSVT, which addresses increased vocal effort and improved sensory perception of effort and is administered in 16 high-effort sessions in one month, has been documented in experimental studies to be a successful approach in the short and long-term. Although the degenerative course of Parkinson's disease cannot be altered at this time, improved oral communication may be an important component in developing the highest levels of functioning and independence for each individual.