Parkinson's disease and unsteadiness

Timothy C. Hain, MD>• Page last modified: March 13, 2021

This page is not intended to review all of Parkinsons but rather just focus on the associations of Parkinson's disease on balance and eye movements. It is written for patients, and not for researchers or clinicians.

Parkinson's disease (PD) is neurological disorder characterized by bradykinesia (slow movement), shuffling gait, postural instability, tremor, and loss of automatic movement. It is due to loss of substantia nigra cells that contain dopamine. It appears that about 50% of cells need to be lost before symptoms appear. Although Parkinsons can be traced to genetic factors, viruses, stroke or toxins such as pesticides in a few individuals, for the most part the cause of Parkinson's in any particular case is unknown (this is called sporadic PD). There are several genetic variants but these account for only about 5% of patients with Parkinsons.

Environmental influences include drinking well water, farming and industrial exposure to heavy metals (e.g. iron, zinc, copper, mercury, magnesium and manganese), alkylated phosphates and organochlorines. Paraquat (a herbicide) has been associated with increased prevalence of Parkinsonism. Several occupations are high risk. Welding is associated with an increased risk vs. the general population of roughly a factor of 10. The prevalence of Parkinsonism is about 1% in welders between 40-69. Cabinet makers and cleaners are also high risk for parkinsonism (Racette et al, 2005).

Cigarette smoking is associated with a decreased incidence. Head trauma increases the risk of Parkinsonism by a ratio ranging from 4.3 to 11 (Bower et al, 2003). The current consensus that Parkinson's might either be caused by an uncommon environmental element combined with high genetic susceptibility or a common environmental element with relatively low susceptibility. Nevertheless, recent work is conflicting suggesting that the genes mentioned above are not associated with sporadic PD (Markopoulo and Langston, 1999).

There is good evidence for genetic factors, but these account for only about 5% of cases. There are both dominant and recessive mutations. As of 2021, there were about 26 genes reported.

Incidence and Prevalence

Parkinson's is uncommon in patients less than 40 years of age. It is found in about 1% of those greater than 50 and 3% of those aged 95 or greater. Every year about 50,000 new cases are diagnosed in the United States. In autopsy studies, Parkinson's is found even more frequently -- about 10% of 70 year olds show evidence of subclinical disease. Prevalence varies greatly throughout the world, ranging from 14/100,000 in China to 328/100,000 in Bombay, India. Asians and African blacks have a lower incidence compared to American blacks and, especially, whites (Lang et al, 1998).

Typical symptoms

They include resting tremor, unsteady gait. slowness of movement (bradykinesia), rigidity, difficulty initiating movement (akinesia), small handwriting (micrographia). Associated symptoms often include seborrhea, orthostatic hypotension, urinary difficulties, constipation, limb pain, depression, dementia (up to 1/3 patients), smelling disturbances (occurs early).

horizontal
Horizontal Saccades in patient with PD

Horizontal saccades in PD are usually normal or nearly normal. There may be more multi-step saccades.

vertical
Vertical Saccades in patient with PD. -- multistep, perhaps slightly slowed.

Ocular symptoms include decreased color discrimination and contrast sensitivity, visual hallucinations, reduced blinking and other problems with eyelid movement, and multistep saccades,(Biousseet al, 2004). Often saccades are slightly slowed. The relative lack of saccade slowing contrasts with PSP, where vertical slowing defines the disease. PSP accounts for just a small fraction of the parkinsonian population.

Orthostatic hypotension may occur associated with the disease or as a complication of medication (Goldstein et al, 2000). The orthostatic hypotension is reported to be due to sympathetic denervation (Goldstein et al, 2002). The lesion involves postganglionic catecholaminergic but not cholinergic nerves (Sharabi et al, 2003). Patients with pure autonomic failure may convert into Parkinsonism or dementia with Lewy bodies, if followed.(Kaufmann et al, 2017)

Impaired olfaction (sense of smell precedes clinical parkinsonism by at least 4 years (Ross et al, 2008)

Patients with Parkinsonism have greater mortality, about 2 times,compared to the general population without PD. This is attributed to greater frailty or reduced mobility (Donnan et al, 2000).

Differential Diagnosis

Diagnosis is mainly clinical and is based on the clinical findings listed above. There are many conditions which may be mistaken for parkinsonism. Among the most common are side effects of drugs (mainly the major tranquilizers such as haloperidol),  strokes involving the basal ganglia, degenerative disorders such as  progressive supranuclear palsy (PSP), corticobasal ganglionic degeneration, olivopontocerebellar degeneration, multiple system atrophy, and Huntington's disease.

The pathological hallmark of Parkinson's disease are Lewy bodies, which are intracytoplasmic inclusion bodies in affected neurons of the substantia nigra. Recently, alpha-synuclein has been identified as the main component of Lewy bodies in sporadic Parkinsonism. Lewy bodies are not found in PSP in abnormal numbers, although they are found in Alzheimer's disease. Lewy bodies, in large numbers, can cause dementia. They are also associated with medication intolerance and visual hallucinations.

Overview of Conventional Treatment for Parkinson's

Nearly all authors agree that treatment with carbidopa-levodopa (Sinemet (TM)) is the single most helpful medication. Levodopa has enabled patients with Parkinsonism to live normal life spans, and greatly ameliorates symptoms in most patients (Ahlskog JE, 1996).

There is presently considerable controversy as to the value of adjunctive agents to levodopa. As a summary, it seems prudent to recommend an approach which incorporates levodopa, direct dopamine agonists, and potential neuroprotective agents such as seligiline. Patients with significant deficits which cannot be adequately treated with drugs may be suitable candidates for surgical approaches.  An algorithm for managing parkinsonism published by the American Academy of Neurology can be found here.

Drug Treatment for Parkinson's

Approaches to PD treatment that probably won't work.

Vasoconstrictors for orthostatic hypotension (such as Midodrine) are unlikely to work for orthostatic hypotension in Parkinsons disease because the lesion involves the post-ganglionic sympathetics (Goldstein et al, 2002).

Late Complications of Parkinson's disease

Surgical therapy

Physical therapy

Prevention

Other sources of information:

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