The 2013 Aspen Course on Parkinson’s Disease and Other Movement Disorders

The 2013 Comprehensive Review of Movement Disorders for the Clinical Practitioner (Aspen Course) marked the 23rd anniversary of this long-standing program on Parkinson’s disease (PD) and other movement disorders. Drs Stanley Fahn, Mark Hallett, and Joseph Jankovic are the course founders and directors. Medscape is pleased to have the highlights of this year’s program discussed in the activity below. The faculty will provide updates on Parkinson’s disease, psychogenic movement disorders, and Huntington’s disease (HD).

A primary goal of the treatment of PD is curing the disease by stopping its progression and restoring the patient to a healthy, normal state. Restoration seems unattainable at present, but slowing disease progression based on the above advances in the basic science of PD seems approachable in the not so distant future. Many attempts at disease modification have been carried out in a number of controlled clinical trials. Most drug trials ended in failure, including trials of coenzyme Q10, creatine, pramipexole, tocopherol, riluzole, and two antiapoptotic agents: TCH346 and CEP-1347. Two controlled surgical trials also failed to slow or reverse PD: intraputaminal infusions of the glial-derived trophic factor (GDNF) and the gene therapy trial of implants of viral vectors containing the gene for neurturin (a member of the GDNF family). So far, only trials of the monoamine oxidase type B inhibitors selegiline[27,28] and rasagiline[29] have provided hints of slowing clinical progression, although a symptomatic effect could possibly account for their benefit. Levodopa was also studied, but interpretation of the results showed incongruity between the clinical and imaging components of the trial.[30] A recent open-label trial suggests that exanatide might have neuroprotective potential.[31] It would be most cost-effective if a suitable animal could be used to test potential neuroprotective agents. As mentioned above, new animal models based on genetics or spread of rogue α-synuclein may prove to be feasible models to study potential neuroprotective agents.

A major development in the clinical understanding of PD is the recognition that the disorder is not simply one marked by motor difficulty (the 6 cardinal features of parkinsonism are tremor-at-rest, bradykinesia, rigidity, loss of postural reflexes, flexed posture, and freezing of gait) but also by the presence of nonmotor features (Table 1).[1] Patients with PD usually have 10 to 12 nonmotor symptoms,[2] some of which often occur several years before the first motor symptom. This is especially true of reduced sense of smell, constipation, and acting out one’s dreams (also known as rapid eye movement [REM] sleep behavior disorder [RBD]). In a 16-year follow-up of men with RBD, 81% developed a parkinsonian disorder with a mean interval of 13 years.[3] Depression and anxiety are also often early features. Cognitive decline with frank dementia is also common, but this condition usually occurs later in the disease course and is more related to the patient’s current age (late 70s through 90s); dementia is eventually seen in up to 80% of patients with PD.[4]

With the typical presentation of insidious onset of unilateral rest tremor and bradykinesia (such as small handwriting, decreased arm swing, and decreased leg swing on walking), the diagnosis is relatively easy. Difficulties arise in distinguishing between tremor of PD and tremor seen in essential tremor; when parkinsonism is present without tremor, raising the possibility of so-called atypical parkinsonism or Parkinson-plus states; and when a gait disorder of a slow shuffling gait with loss of balance is observed. The tremor of essential tremor differs from that of PD in that the former is a tremor of action. This can be seen with writing, including the drawing of Archimedes’ spiral, or with the finger-to-nose maneuver. Occasionally a patient may have both conditions, so the diagnosis can be initially puzzling. The neuroimaging procedure known as DaTscan can help distinguish between the two conditions. DaTscan is a single photon emission computer tomography (SPECT) scan in which the radioligand binds to the dopamine transporter that is located on the dopamine nerve terminals in the striatum. In PD, there is asymmetrical loss of the nerve terminals, and hence, an asymmetrical reduction is detected in the DaTscan. In essential tremor there is no loss of radioligand binding. Although this SPECT scan can be helpful in differentiating between the two conditions, the scan is sometimes difficult to interpret and expertise is required.[5]

The DaTscan is not helpful in distinguishing between PD and Parkinson-plus syndromes (progressive supranuclear palsy, multiple system atrophy, and cortical basal syndromes) because all of these have striatal dopamine deficiency. The presence of additional neurologic signs -- such as ocular involvement, orthostasis and other forms of dysautonomia, early freezing of gait, early falling, and lack of dramatic response to levodopa therapy – is a clue that the patient may have a Parkinson-plus disorder. A slow, short-stride gait with falling or fear of falling is a common gait disorder. This can sometimes be the onset of PD, but often it is due to cerebrovascular insufficiency (vascular parkinsonism), normal pressure hydrocephalus, or a poorly understood syndrome of senile gait disorder. These conditions do not respond well to levodopa, but this medication could be tried to make sure the patient does not have an unusual presentation of PD. READ MORE