LA CONSULTA SEMANAL

CONSULTA

1: Drugs  2002;62(5):775-86

Emerging therapies in the pharmacological treatment of Parkinson's disease.

Korczyn AD, Nussbaum M.

Department of Neurology, Sackler School of Medicine, Tel-Aviv University Medical School, Ramat-Aviv, Israel.

The pharmacological management of Parkinson's disease is a complex and dynamic task; there is no one 'right' strategy indicating which drugs should be used at a particular stage of the disease. There are now many different drugs belonging to several classes that may be effective, and there are still differences of opinion among leading clinicians about the best course of treatment. This review focuses on drug therapy for the motor impairment in Parkinson's disease. Current and future research directions are summarised by taking inventory of recent and innovative areas of development in the field, representing each category with at least one of its featured treatments. The main research efforts are being directed towards delaying the use of levodopa or finding therapies to be used as adjunct to it, in order to postpone motor complications and, in particular, dyskinesias. One of the recent trends is early employment of dopamine agonists. Additional efforts are being directed towards protecting and restoring dopamine neurons. Novel therapies acting on non-dopaminergic systems are also being researched.

2: Geriatrics  2002 Mar;57(3):46-50 [Texto completo en formato PDF]

Parkinson's disease. Therapeutic strategies to improve patient function and quality of life.

Danisi F.

Mount Sinai School of Medicine, New York, NY, USA.

Idiopathic Parkinson's disease (PD) is an age-related neuro-degenerative disorder characterized by slowness, stiffness, resting tremor, gait impairment, and postural instability. Levodopa is the most potent pharmacologic agent for symptom management and is associated with an increase in quality of life and longevity for patients with PD, but chronic use causes motor complications. The availability of several newer types of agents--dopamine agonists, monoamine oxidase inhibitors, and catechol-O-methyltransferase inhibitors—gives physicians increased flexibility with regard to first-line therapy, adjunct therapy, and managing or reducing the frequency of motor complications and other side effects associated with chronic levodopa therapy.

Publication Types:

Review

3: Neurology  2002 Jan 22;58(2):179-85

Recent advances in the genetics and pathogenesis of Parkinson disease.

Mouradian MM.

Genetic Pharmacology Unit, Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-1406, USA. MouradianM@ninds.nih.gov

The identification of three genes and several additional loci associated with inherited forms of levodopa-responsive PD has confirmed that this is not a single disorder. Yet, analyses of the structure and function of these gene products point to the critical role of protein aggregation in dopaminergic neurons of the substantia nigra as the common mechanism leading to neurodegeneration in all known forms of this disease. The three specific genes identified to date--alpha-synuclein, Parkin, and ubiquitin C terminal hydrolase L1--are either closely involved in the proper functioning of the ubiquitin-proteasome pathway or are degraded by this protein-clearing machinery of cells. Knowledge gained from genetically transmitted PD also has clear implications for nonfamilial forms of the disease. Lewy bodies, even in sporadic PD, contain these three gene products, particularly abundant amounts of fibrillar alpha-synuclein. Increased aggregation of alpha-synuclein by oxidative stress, as well as oxidant-induced proteasomal dysfunction, link genetic and potential environmental factors in the onset and progression of the disease. The biochemical and molecular cascades elucidated from genetic studies in PD can provide novel targets for curative therapies.

Publication Types:

4: Postgrad Med  2001 Dec;110(6):15-8, 21-3, 28 [Texto completo]

Management of Parkinson's disease. Strategies, pitfalls, and future directions.

Hermanowicz N.

Department of Neurology, Movement Disorders Program, University of California, Irvine, College of Medicine, 105 Irvine Hall, Irvine, CA 92697, USA. nhermano@uci.edu

In coming years Parkinson's disease will become increasingly prevalent as the baby boom generation grows older. Diagnosis often is complicated and requires careful consideration of symptoms and neurologic findings. Optimal symptomatic treatment of Parkinson's disease involves an individualized approach with each patient and ongoing evaluation of benefits versus side effects. Neurosurgical intervention is an option for some patients who are not adequately helped by medical therapy. New treatments (e.g., stem cell therapy) are currently being studied and may be available in the foreseeable future.

Publication Types:

Review

5: JAMA  2001 Dec 26;286(24):3056-9

Surgical treatment of Parkinson disease.

Eskandar EN, Cosgrove GR, Shinobu LA.

Massachusetts General Hospital, 15 Parkman St, ACC #331, Boston, MA 02114. cosgrove@helix.mgh.harvard.edu

Publication Types:

Review

6: J Neurol  2001 Sep;248 Suppl 3:III28-31

Drug-induced psychotic symptoms in Parkinson's disease. Problems, management and dilemma.

Kuzuhara S.

Department of Neurology, Mie University School of Medicine, Tsu, Mie-ken, Japan. kuzuhara@clin.medic.mie-u.ac.jp

Psychotic symptoms develop in 20-30% of patients with Parkinson's disease (PD) receiving chronic anti-PD medications, and visual hallucinations with or without delirium and paranoid delusions are the most frequent symptoms. Psychotic symptoms disturb ADL and QOL of PD patients and tax caregivers far more than the motor disabilities do, and good management of drug-induced psychotic symptoms is potentially important. Withdrawal of anti-PD drugs relieves the patients from psychotic side effects, but worsens the parkinsonian motor symptoms. The first step of treatment is to eliminate triggering factors other than anti-PD drugs, such as infections, metabolic disorders, subdural hematoma, and hallucinogenic drugs. The second step is to eliminate anti-PD drugs in the following order; first anticholinergics, amantadine and selegiline, second dopamine agonists, and finally levodopa/carbidopa. Anti-PD medications should be reduced to the point of improving psychotic side effects without drastically worsening parkinsonian motor symptoms. When the above adjustments fail to sufficiently alleviate psychotic side effects, the third step is consideration of antipsychotic drugs although they have potential capacity to antagonize dopamine D2 receptors and worsen parkinsonism. Atypical antipsychotics such as clozapine and olanzapine are recommended, though the former is not available in Japan.

Publication Types:

Review

7: J Neurol  2001 Sep;248 Suppl 3:III22-7

Intrinsic and extrinsic psychosis in Parkinson's disease.

Wolters EC.

Graduate School for Neurosciences, Amsterdam VUMC Vrije Universiteit Medical Center, Department of Neurology, The Netherlands.

Direct and indirect signs and symptoms of Parkinson's disease are a major cause of disability in the elderly. Intrinsic symptoms comprise not only the well-known clinical hallmarks of this disease with motor behavioral abnormalities, such as bradykinesia, hypokinesia, rigidity and tremor, but also autonomic failure with orthostatic hypotension, urinal incontinence and impotence as well as non-motor behavioral abnormalities: mental dysfunction characterized by mood disorders, cognitive dysfunction and, sporadically, delusions and hallucinations. These symptoms are caused by a progressive abnormal degeneration of the dopamine (DA) producing cells in the substantia nigra (SN) and ventral tegmentum area (VTA) in combination with an interindividual fluctuating degree of decay in the noradrenergic (locus coeruleus), cholinergic forebrain (nucleus basalis of Meynert) and serotoninergic (dorsal raphe nuclei) systems. Extrinsic symptoms, induced by pharmacotherapy, mainly manifest with (un)predictable motor response fluctuations and dopaminomimetic psychosis. Psychological and psychiatric symptoms in Parkinson's disease (PD) are important predictors of the patient's quality of life. As these symptoms are potentially treatable, identification is of major clinical importance both for the patients and their caregivers and may enable to maintain Parkinson's disease patients at home for a longer period.

Publication Types:

Review

8: J Neurol  2001 Sep;248 Suppl 3:III12-21

Treatment options for depression and psychosis in Parkinson's disease.

Poewe W, Seppi K.

Department of Neurology, University Hospital Innsbruck, Austria. werner.poewe@uibk.ac.at

Neuropsychiatric symptoms are a frequent feature of advancing Parkinson's disease (PD). The reported prevalence of depression varies greatly between different studies but there is general consensus that between 40 and 50% of patients will be affected. Depression may antedate motor manifestations of Parkinson's disease and is usually of moderate or mild intensity. However, depression is of major impact on the quality of life in PD patients according to a recent survey. Drug-induced psychosis is one of the major therapeutic challenges in Parkinson's disease and may occur in up to 6% in otherwise uncomplicated de novo patients when first receiving dopaminergic therapy. It increases in frequency, in advanced disease and particularly in patients with dementia where up to 22% may be affected. There is an amazing lack of controlled clinical trials assessing the effects of antidepressants in clinical trials including more than 20 patients and assessing efficacy of antidepressants specifically in the context of mood changes in Parkinson's disease. A comprehensive literature search yielded only a total of 17 articles of which a majority included less than 20 patients and/or did not use valid depression ratings. The only randomized controlled trial was conducted more than 20 years ago using nortryptiline while no controlled trials were available on the use of serotonin reuptake inhibitors. Studies assessing the antidepressant action of dopaminergic therapies are few and inconclusive. Thus, while tricyclic antidepressants or SSRIs are widely used in clinical practice, there is still a need for controlled clinical trials proving their efficacy specifically in parkinsonian depression. Three randomized controlled trials are now available assessing the efficacy of the atypical neuroleptics clozapine and olanzapine in the treatment of drug-induced psychosis. While clozapine is of proven efficacy at least in the short-term management of this complication without negative impact on the motor symptoms, olanzapine in currently used doses of 2.5 to 15 mg/d seems to aggravate motor symptoms with lesser effect on psychosis compared to clozapine. Currently, clozapine is the atypical neuroleptic of choice for the treatment of drug-induced psychosis in Parkinson's disease.

Publication Types:

Review

9: J Neurol  2001 Sep;248 Suppl 3:III1-4

Dementia in Parkinson's disease.

Korczyn AD.

Sackler Faculty of Medicine, Tel-Aviv University Medical School, Ramat-Aviv, Israel. neuro13@post.tau.ac.il

Advanced Parkinson's disease (PD) is frequently associated with dementia. The pathogenesis of this dementia is complex, related to deficiency of several biogenic amines and cortical Lewy body deposition, as well as co-existent age-related brain changes, both of the Alzheimer's type and vascular. However, degeneration of the cholinergic neurons in the nucleus basalis of Meynert may have an important contribution to the cognitive decline. The dementia of PD has a grave effect on the quality of life of the patients and their caregivers, as well as negative effect on their survival. The treatment of dementia associated with PD therefore must encompass several agents. We have treated several patients with the cholinesterase inhibitor rivastigmine which produced gratifying results. Future studies should define the exact role of this agent in the treatment of the dementia of PD.

Publication Types:

Review

10: Neurol Clin  2001 Aug;19(3):607-27, vi

Lumping and splitting the Parkinson Plus syndromes: dementia with Lewy bodies, multiple system atrophy, progressive supranuclear palsy, and cortical-basal ganglionic degeneration.

Mark MH.

Department of Neurology, Robert Wood Johnson Medical School, New Brunswick, New Jersey 08901, USA. mark@umdnj.edu

The atypical parkinsonian or Parkinson Plus syndromes are often difficult to differentiate from Parkinson's disease and each other. In this article, the clinicopathological characteristics of dementia with Lewy bodies, multiple system atrophy, progressive supranuclear palsy, and cortical-basal ganglionic degeneration are discussed. These disorders, although clinically distinct, may have more similarities than previously thought, based on modern immunocytochemical techniques and new genetic findings. These intriguing interconnections at a basic molecular level have provided the scientific rationale for lumping these diseases into two groups, the synucleinopathies and the tauopathies.

Publication Types:

Review

11: Neurol Clin  2001 Aug;19(3):579-605, vi

Parkinson's disease: medical and surgical treatment.

Ahlskog JE.

Department of Neurology, Mayo Medical School, Chair, Mayo Clinic Division of Movement Disorders, Mayo Clinic, Rochester, Minnesota 55905, USA.

It has been over three decades since the introduction of L-dihydroxyphenylalanine or levodopa therapy for Parkinson's disease (PD). The early levodopa trials were driven by recognition of a profound cerebral dopamine deficiency state in this disorder. Whereas dopamine fails to cross the blood brain barrier and hence is ineffective as therapy, the amino acid precursor, dopa, is transported across this barrier and provides a substrate for dopamine synthesis. Levodopa is converted to dopamine within the brain by dopa decarboxylase, replenishing central dopamine stores and potentially reversing the motor symptoms of PD.

Publication Types:

Review

12: Hosp Med  2001 Aug;62(8):456-70

Updated guidelines for the management of Parkinson's disease.

Bhatia K, Brooks DJ, Burn DJ, Clarke CE, Grosset DG, MacMahon DG, Playfer J, Schapira AH, Stewart D, Williams AC;  Parkinson's Disease Consensus Working Group.

University Department of Clinical Neurology, Institute of Neurology, London.

New data on diagnosis, drug therapy, surgery and psychosocial concerns have emerged since the publication of the 1998 Guidelines for the Management of Parkinson's Disease. This article reviews new data and addresses issues left unanswered in the previous guidelines.

Publication Types:

Review

13: Geriatrics  2001 Aug;56(8):24-5, 29-30, 33-5 [Texto completo en formato PDF]

Parkinson's disease. Update in diagnosis and symptom management.

Marjama-Lyons JM, Koller WC.

Department of Neurology, Parkinson's Center, University of Florida at Shands Jacksonville, Jacksonville, FL, USA.

Parkinson's disease (PD) is a progressive neurodegenerative disorder with a high burden of morbidity. Because no diagnostic test exists for PD, clinical knowledge and skill are key to making an early, accurate diagnosis. Diagnostic criteria for PD require at least two of three motor signs: tremor, rigidity, or bradykinesia. Levodopa and the dopamine agonists are considered first-line drug therapy. Recent studies have shown a lower incidence of dyskinesia in patients who began therapy with a dopamine agonist, although levodopa may be better tolerated by patients age 70 or older. Combinations of medications and rehabilitative, alternative, and surgical therapies can often help patients achieve adequate control of PD motor symptoms and maintain a high quality of independent living.

Publication Types:

Review

14: Hosp Pract (Off Ed)  2001 Jun 15;36(6):27-32, 41 [Texto completo]

Advances in managing Parkinson's disease.

Waters CH.

Columbia University, College of Physicians and Surgeons, New York, NY, USA.

The medical choices are now more numerous: Dopamine agonists may have value not only for addressing the motor fluctuations of levodopa therapy but also for deferring the use of levodopa. Surgical choices are bolstered by the addition of investigational options such as neuronal transplantation, in addition to options currently approved, such as pallidotomy.