Motor Disorder

The Parkinson's-Reversing Breakthrough

Treatment Options for Parkinsons

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General Approach

Because the results of drug treatment for the motor disorder of MSA are generally poor, other therapies are all the more important. Physiotherapy helps maintain mobility and prevent contractures, and speech therapy can improve speech and swallowing and provide communication aids. Dysphagia may require feeding via a nasogastric tube or even percutaneous endoscopic gastrostomy (PEG). Occupational therapy helps to limit the handicap resulting from the patient's disabilities and should include a home visit. Provision of a wheelchair is usually dictated by the liability to falls because of postural instability and gait ataxia but not by akinesia and rigidity per se. Psychological support for patients and partners needs to be stressed.

Parkinsonism

Parkinsonism is the predominant motor disorder in MSA and therefore represents a major target for therapeutic intervention. Although less effective than in PD and despite the lack of randomized-controlled trials, levodopa replacement represents the mainstay of anti-parkinsonian therapy in MSA. Open-label studies suggest that up to 30-40% of MSA patients may derive benefit from levodopa at least transiently (13,26). Occasionally, a beneficial effect is evident only when seemingly unresponsive patients deteriorate after levodopa withdrawal (25). Preexisting orthostatic hypotension is often unmasked or exacerbated in levodopa-treated MSA patients associated with autonomic failure. In contrast, psychiatric or toxic confusional states appear to be less common than in PD (13). Results with dopamine agonists have been even more disappointing (194). Severe psychiatric side effects occurred in a double-blind crossover trial of six patients on lisuride, with nightmares, visual hallucinations, and toxic confusional states (195). Wenning et al. (13) reported a response to oral dopamine agonists only in 4 of 41 patients. None of 30 patients receiving bromocriptine improved, but 3 of 10 who received pergolide had some benefit. Twenty-two percent of the levodopa responders had good or excellent response to at least one orally active dopamine agonist in addition. Anti-parkinsonian effects were noted in 4 of 26 MSA patients treated with amantadine (13), however, there was no significant improvement in an open study of 9 patients with atypical parkinsonism, including 5 subjects with MSA (196).

Blepharospasm as well as limb dystonia, but not antecollis, may respond well to local injections of botulinum toxin A.

Ablative neurosurgical procedures such as medial pallidotomy fail to improve parkinsonian motor disturbance in MSA (197). However, most recently a beneficial short-term and long-term effect of bilateral subthalamic nucleus high-frequency stimulation has been reported in four patients with MSA-P (198). Further studies are needed to establish the scope of deep brain stimulation in MSA.

Cerebellar Ataxia

There is no effective therapy for the progressive ataxia of MSA-C. Occasional successes have been reported with cholinergic drugs, amantadine, 5-hydroxytryptophan, isoniazid, baclofen, and propanolol; for the large majority of patients these drugs proved to be ineffective.

One intriguing observation is the apparent temporary exacerbation of ataxia by cigarette smoking (199,200). Nicotine is known to increase the release of acetylcholine in many areas of the brain and probably also releases noradrenaline, dopamine, 5-hydroxytryptophan, and other neurotransmitters. Nicotinic systems may therefore play a role in cerebellar function and trials of nicotinic antagonists such as dihydro-p-erythroidine might be worthwhile in MSA-C.

Practical Therapy

Because of the small number of randomized controlled trials, the practical management of MSA is largely based on empirical evidence (o) or single randomized studies (T), except for three randomized controlled trials of midodrine (TT) (178-180). The present recommendations are summarized in Table 3.

Future Therapies

Two European research initiatives—European MSA-Study Group (EMSA-SG) and Neuroprotection and Natural History in Parkinson Plus Syndromes (NNIPPS)—are presently conducting multicentre intervention trials in MSA using candidate neuroprotective agents. For the first time, prospective progression data using novel rating tools such as the Unified MSA Rating Scale (UMSARS) (201) will become available. Furthermore, surrogate markers of disease progression will be evaluated using structural and functional neuroimaging. Even if the ongoing trials are negative, they will certainly stimulate further trial activity in MSA, which is desperately needed to tame this "beast."

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A Disquistion On The Evils Of Using Tobacco

A Disquistion On The Evils Of Using Tobacco

Among the evils which a vitiated appetite has fastened upon mankind, those that arise from the use of Tobacco hold a prominent place, and call loudly for reform. We pity the poor Chinese, who stupifies body and mind with opium, and the wretched Hindoo, who is under a similar slavery to his favorite plant, the Betel but we present the humiliating spectacle of an enlightened and christian nation, wasting annually more than twenty-five millions of dollars, and destroying the health and the lives of thousands, by a practice not at all less degrading than that of the Chinese or Hindoo.

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