Ayurvedic Medicine

Ayurvedic medicine is the traditional medical system in India, which has existed for over 5000 years. The term Ayurveda literally means science of life or life knowledge. PD is documented to have existed in ancient India and was called Kampavata. Similar to the TCM system, physical illness is thought to result from emotional imbalance, unhealthy lifestyle, and toxins that ultimately upset the balance of the three doshas or regulatory systems of a person (5). These three doshas are vata, which...

Globus Pallidus Internal Segment Suppression Theory

This theory posits that the loss of SNpc dopamine neurons causes decreased activity in the striatal neurons of the direct pathway. This results in a reduction of inhibition of GPi neurons, which in turn results in increased inhibition of the VL thalamus and a reduction of excitation of the MC and SMA, thus providing an explanation of loss and slowing of movements (Fig. 1). Loss of SNpc dopaminergic drive to striatal neurons of the indirect pathway results in decreased inhibition of these...

Clinical Uses

Since the advent of levodopa therapy for PD in the 1960s, the usefulness and popularity of anticholinergics waned dramatically. However, an evidence-based review by the Cochrane Collaboration concluded that anticholinergics are effective in improving motor function in parkinsonian patients as monotherapy and adjunct therapy. Current data are not sufficient to allow comparison in efficacy or tolerability between individual anticholinergic medications (76). Tremor Predominant Parkinson's Disease...

Parkin Gene Therapy

The apparent success of gene therapy in conferring novel capabilities to nigral and striatal cells has led some researchers to question if the pathology underlying PD can be reversed in a more physiologic manner. Genetic analyses of PD families have demonstrated a number of genes linked to the disease. These mutations seem to share a role in intracellular housekeeping and the processing of intracellular protein residue. It is estimated that approximately 0.4 to 0.7 of patients diagnosed with...

Pathophysiology of Psychosis and Risk Factors

The pathophysiology of psychosis in PD is poorly understood, but dopaminergic and serotonergic mechanisms have been proposed. One theory is that chronic excessive stimulation of dopamine receptors, particularly in the mesolimbic mesocorti-cal pathways, causes hypersensitization, resulting in psychosis when patients are treated with dopaminergic agents (36). However, exogenous dopamine supplementation by itself is not the only factor in the development of psychosis since all PD medications...

Guam Parkinsondementia Complex

A characteristic parkinsonism with dementia Parkinson dementia complex (PDC) with a number of features that overlap with PSP (50) has been reported in the native Chamorro population of Guam since the 1950s (51). The frequency of PDC is declining in recent years for unknown reasons, and the etiology is unknown. The gross findings in PDC are notable for cortical atrophy affecting frontal and temporal lobes, as well as atrophy of the hippocampus and the tegmentum of the rostral brainstem (52)....

Other Nineteenth Century Contributions

FIGURE 20 Dysautonomia in Parkinson's disease. This drawing by Daniel Vierge (1851-1904) shows the Salpetriere inpatient wards with a single central furnace for heat (18). In this context, Charcot recognized the distinctive dysautonomia of Parkinson's disease, noting how patients experienced a sense of hyperthermia even in the drafty, cold wards of the French hospitals FIGURE 20 Dysautonomia in Parkinson's disease. This drawing by Daniel Vierge (1851-1904) shows the Salpetriere inpatient wards...

Vesicular Monoamine Transporter And Dopamine Transporters In The Substantia Nigra Pars Compacta

Vesicular transporters transport neurotransmitters into vesicles of nerve terminals and neuroendocrine cells and make them available for regulated release. VMAT1 is localized predominantly in the neuroendocrine cells, whereas VMAT2 is widely distributed in monoaminergic terminals and dendrites. In the dopaminergic nerve terminal, VMAT2 transports cytoplasmic dopamine and 1-methyl-4-phenylpyridium (MPP+) into the vesicles (16). Dopamine that is not incorporated into the vesicles gets oxidized...

References

Quinn NP, Luthert P, Hanover M, Marsden CD. Pure akinesia due to Lewy body. Parkinson's disease a case with pathology. Mov Disord 1989 4 885-892. 2. Rajput AH. Pathologic and biochemical studies of juvenile parkinsonism linked tochro-mosome 6q. Neurology1999 53(6) 1375. 3. Klein C, Pramstaller PP, Kis B, et al. Parkin deletions in a family with adult-onset, tremor-dominant parkinsonism expanding the phenotype. Ann Neurol 2000 48(1) 65-71. 4. Polymeropoulos MH. Autosomal dominant Parkinson's...

Herbs

A variety of herbs may be useful to treat the motor symptoms of PD as well as some of the associated symptoms or possible side effects from PD medications (14). Mucuna pruriens is a natural plant, indigenous to India, which contains levodopa. It is also called kawach, cowage, cowhage, or velvet bean. It has been studied extensively and shown to reduce the motor symptoms of PD similar to carbidopa lev-odopa (15). In fact, mucuna seeds have been prescribed by Ayurvedic physicians in India for...

Levodopa Challenge Test

It can be difficult to accurately differentiate PD from other forms of parkinsonism, especially during the early stages of disease. Levodopa administration can be used for diagnostic purposes, as PD patients respond more frequently and robustly to levodopa compared with other forms of parkinsonism. Clarke and Davies (145) reviewed 13 studies that examined whether an acute levodopa or apomorphine challenge test could aid in the diagnosis of PD. Four studies examined de novo patients and nine...

Unilateral Subthalamic Nucleotomy

The occurrence of cognitive deficits that have been reported with thalamotomy and pallidotomy, and the failure of thalamotomy to improve features other than tremor, has driven an interest in trying to find alternative targets to lesion, especially for patients who require bilateral procedures and are not suitable for DBS. The realization that the neurons of the STN in parkinsonian monkeys are over-active led to an interest in this nucleus as a possible target for PD (98). Surgeons had...

Freezing And Other Gait Abnormalities

A slow, shuffling, narrow-based gait is one of the most characteristic features of PD (83). The parkinsonian gait reveals certain features that overlap with the gait disturbance associated with normal pressure hydrocephalus (84,85). In a study of 50 subjects older than 70 years, Sudarsky and Ronthal (86) established a principal cause of the gait disorder in all but seven subjects (essential gait disorder). They, but not others (87), suggested that this senile gait is related to normal pressure...

Does Tolerance Develop to Levodopa

The lay literature is replete with information suggesting that levodopa loses its effect after about five years. This leads to some trepidation on the part of the patient and physician in initiating therapy. If that were the case, it would indicate that tolerance is a possible concern and would argue for delaying treatment. It is conceivable that, when all nigrostriatal cells are depleted, levodopa would lose all effectiveness since these are the cells that convert levodopa and release...

Motor Fluctuations And Dyskinesia Definitions

There is a loss of 50 to 60 of nigrostriatal neurons or a reduction in striatal dopamine concentrations of approximately 70 associated with the onset of clinical symptoms of PD (24). The surviving neurons can initially compensate with increased dopamine synthesis, but subsequently, with continued disease progression and neuronal loss, these mechanisms fail. What follows is the loss of the ability of nigrostri-atal neurons to store and release dopamine appropriately, followed by postsynaptic...

Kelly E Lyons and Rajesh Pahwa

Department of Neurology, University of Kansas Medical Center, Kansas City, Kansas, U.S.A. Stereotactic surgeries for movement disorders were introduced in the late 1940s (1-3) but were not widely accepted due to significant morbidity, mortality, and limited knowledge of the appropriate target for symptomatic benefit. With advances in pharmacological therapy, particularly the availability of levodopa, these surgeries were rarely performed for Parkinson's disease (PD) until the late 1980s (4)....

Postencephalitic Parkinsonism

Parkinsonism following encephalitis lethargica during the influenza pandemic between 1916 and 1926 is known as postencephalitic parkinsonism (PEP). During the recovery phase of the acute viral encephalitis, parkinsonian rigidity developed with the most characteristic clinical features being oculogyric crises. The PEP brain has NFTs in the cortex, basal ganglia, thalamus, hypothalamus, substantia nigra, brainstem tegmentum, and cerebellar dentate nucleus (48). The distribution of the pathology...

Levodopa Methyl Ester

Levodopa methyl-ester carbidopa effervescent tablets (CNP-1512) are currently approved for rescue therapy in PD in Italy (Chiesi Farmaceutici). Outside of Italy, the drug (V1512) is owned by Vernalis Pharmaceuticals. This preparation is approximately 250 times more soluble in water and can thus be easily dissolved and orally administered. Studies comparing the drug with standard levodopa preparations demonstrate a faster onset of action (by a mean of 8.5 minutes) and a longer total duration of...

Respiratory Dysfunction in Parkinsons Disease

A number of studies have provided evidence, through various aerodynamic measurements, for disordered respiratory function in individuals with PD. These disorders include reduced vital capacity, reduced total amount of air expended during maximum phonation tasks, reduced intraoral air pressure during consonant vowel productions, and abnormal airflow patterns (48-50). The origins of these airflow abnormalities are not clear but they may be related to variations in airflow resistance due to...