For decades, the foundations of idiopathic Parkinson’s syndrome treatment have remained unshaken. Nevertheless, research into this clinical picture has, of course, by no means come to a standstill. It is worth taking another closer look at the current diagnostic and therapeutic options.
After Alzheimer’s disease, Parkinson’s is the second most common neurodegenerative disease. The prevalence of idiopathic Parkinson’s syndrome is 160-180/100,000 in Central Europe, increasing with age (713/100,000 in those over 65 years of age). On average, sufferers develop the disease at the age of 61. However, there is also juvenile Parkinson’s (under 21 years of age) as well as the classification into “young onset”, “late onset” and “very late onset” Parkinson’s (<40 y., >40 y., >75 J.). The majority of all diseases, namely up to 80%, are idiopathic, followed by secondary forms, which may be vascular, drug-related (neuroleptics) or toxic (heavy metals). Atypical Parkinson’s syndromes in the course of multisystem atrophy, Lewy body disease or progressive supranuclear palsy are much rarer – fortunately, because here basically no effective therapy exists at all, since the response to L-DOPA is poor and the survival time is significantly shorter.
Diagnosis of idiopathic Parkinson’s syndrome
In the prodromal stage, non-motor symptoms may occur in addition to motor symptoms (Table 1). These precede diagnosis by up to ten years, but usually by three to six years. The important factor is depression, which is present in a good fifth at this time and in almost half of those affected overall (prevalence: 40%). Also characteristic is the so-called “REM-sleep behavior disorder”, i.e. the nocturnal acting out of dreams (in at least 30-60% of cases). The disorder may occur before the onset of extrapyramidal motor symptoms; after twelve years, approximately one-third of individuals develop Parkinson’s syndrome. Autonomic/vegetative symptoms are more commonly known from later stages of the disease, but they sometimes precede the disease.
The most important symptom in the clinical stage that eventually leads to diagnosis is akinesia (impoverishment of movement with slowing and reduction of movement amplitude). Previously, the diagnosis consisted of this and one of three symptoms: rigor (increased muscle tension, independent of passive movement speed), tremor (resting tremor, asymmetric, usually hands, rarely head or chin), and postural instability (disturbance of balance-regulating reflexes, postural instability). Today, it is supplemented by a standardized olfactory test and the inclusion of non-motor symptoms, as well as imaging procedures such as DAT scan of the brain and MIBG-SPECT of the heart, if necessary. Supportive diagnostic factors include a good response to L-DOPA and onset at the upper extremity.
The absolute exclusion criteria of idiopathic parkinsonian syndrome include:
- Cerebellar symptoms
- Supranuclear gaze palsy
- Lower extremity symptoms only >3 years
- No response to L-DOPA
- Clear sensory cortical symptoms (apraxia, aphasia, etc.).
- Normal DAT scan.
Therapy – the revolution is a long time coming
Still no drug exists that slows disease progression. After 50 years, L-DOPA is still the most effective drug for treating motor symptoms. However, after five to ten years at the latest, the so-called “honeymoon phase” with very good efficacy and few side effects, motor fluctuations, loss of efficacy and dyskinesias occur in all patients. Therefore, its use is primarily indicated in elderly patients over 70 years of age. Younger patients – and this means all those affected under the age of 70 – can initially still benefit from dopamine agonists such as pramipexole, ropinirole or rotigotine as monotherapy. If L-DOPA is still necessary here, it is given early only in the low dose of 4 mg/kgKG or 5 mg/kgKG (depending on gender). L-DOPA therapy can lead to vitamin B12 deficiency, resulting in polyneuropathies.
In general, the side effects and loss of efficacy of long-term therapy are addressed by dose reduction and addition of COMT inhibitors such as entacapone or tolcapone, dopamine agonists, and amantadine. The latter has been on the market for a very long time. In case of impossibility of food intake in the hospital, the formulation as infusion is practical. Amantadine is now available in a sustained release form with good efficacy against dyskinesia – but not yet in Switzerland. Other news include IPX066 (USA: RytaryTM), a sustained-release formulation of levodopa-carbidopa, or safinamide (Xadago®, since late 2015), an MAO-B inhibitor with simultaneous modulation of glutamate release. However, a real revolution in the treatment of Parkinson’s disease is still not in sight.
Escalation
Patients under the age of approximately 65-70 years without dementia or severe mental/somatic illness, but with symptoms that (still) respond to L-DOPA, may be offered deep brain stimulation. Their effect also unfolds in motor fluctuations and dyskinesias that cannot be treated with medication, severe tremor and camptocormia (forward bending of the trunk). The stimulation of the Nc. subthalamicus and the globus pallidus internus is equivalent here. This is a (reversible) surgical procedure with corresponding risks.
Quite new and almost to be called “hype” is (MRI-guided) functional ultrasound neurosurgery. Ultimately, comparable to a thalamotomy or pallidotomy, it relies on the destruction of brain tissue (similar potential side effects, irreversible), but without incision and with reduced to nonexistent risk of infection/bleeding. This focused ultrasound technology does not lead to a “cure” any more than other therapy methods.
Another option for escalation is intrajejunal levodopagel via pump. This prolongs on-time and reduces dyskinesias, but requires a specialized center nearby, which is not ideal for rural populations. Subcutaneous apomorphine (dopamine agonist) may also be used, either as a subcutaneous injection (pen) to shorten off-duration or as a continuous subcutaneous infusion (pump) for the purpose of improving dyskinesias and off-time.
Non-medicinal approaches – From physiotherapy to occupational therapy
Significant improvement in gait speed, gait block, balance, movement amplitude/initiation, mobility, and independence is achieved through physical therapy. It has no influence on the frequency of falls and quality of life. In the early stages, sports, Nordic walking, Tai Chi or “exergaming” (training through electronic games) can be helpful; in the middle stages, thrust training, anti-freezing and rhythmic training come into play; in the late stages, it is finally a matter of preserving residual functions, transfer training and provision of aids.
For slurred speech, speech therapy improves voice volume, range, intelligibility, and dysphagia.
Occupational therapy, as always, is designed to improve Activities of Daily Living (ADL).
Source: Internal Medicine Update Refresher, June 20-24, 2017, Zurich.
