© Springer-Verlag Italia 2015
Angelo Sghirlanzoni, Giuseppe Lauria and Luisa Chiapparini (eds.)Prognosis of Neurological Diseases10.1007/978-88-470-5755-5_2828. Extrapyramidal Diseases: Parkinson’s Disease
(1)
U.O.C. Neurologia – Ospedale Generale Regionale “F. Miulli”, Acquaviva delle Fonti, Bari, Italy
Keywords
Neurodegenerative diseaseParkinson’s diseasePrognosis of ParkinsonPremotor symptoms of ParkinsonLevodopa responseLevodopa nonresponsive symptomsParkinsonismKey Facts
Definitions and clinical features – PD is a movement disorder characterized by asymmetric tremor, bradykinesia, rigidity, and postural instability
Diagnosis – Clinical findings, including good and sustained response to levodopa
Laboratory
–Genetics – More than 15 AD and AR genes have been associated with PD
Imaging – SPECT with DaT-scan may contribute to diagnosis
Top Differential Diagnoses – Essential tremor; degenerative, vascular, toxic parkinsonisms; normal pressure hydrocephalus
Prognosis
Principles of treatment – Levodopa is the golden standard in PD treatment. Deep brain stimulation of the subthalamic nucleus can improve PD.
Disability – May differ in the many phenotypic subtypes of PD. Cumulative general surveys indicate that 30 % of patients would lose their job within 1 year, and most after 5 years of disease. Cognitive impairment predicts more severe motor impairment and disability.
Abbreviations
AD, autosomal dominant; AR, autosomal recessive; CBD, Cortico-basal degeneration; GBA, Glucocerebrosidase; LBD, Lewy body dementia; MMSE, Mini Mental State Examination; MSA, multiple system atrophy; PAF, pure autonomic failure; PIGD, postural instability/gait difficulty; PD, Parkinson’s disease; PSP, progressive supernuclear palsy; QoL, Quality of life; RBD, REM-sleep behavior disorders; SMR, Standardized mortality ratio; DBS, Deep brain stimulation; STN, Subthalamic nucleus; UPDRS-ME Unified Parkinson’s Disease Rating Scale-Motor Examination
28.1 Definition and Clinical Features
Parkinson’s disease (PD) is a common neurodegenerative condition that usually presents with asymmetric tremor, bradykinesia, rigidity, and postural instability. A range of nonmotor symptoms – sleep and mood disorders, constipation, and smell alteration – may precede, even by decades, the onset of PD. The efficacy of the treatment changes over years due to the progressive nature of disease course, leading to the advanced phase of the disease.
28.2 Diagnosis
A good to excellent response to levodopa has a diagnostic value (ex juvantibus diagnosis).
28.3 Epidemiology
PD prevalence, second among neurodegenerative diseases, rises with age; it is more common in males than in females and in developed countries affects around 2 % of the population over 65.
Genetics
Although more than 15 identified genes and genetic loci have been associated with PD, they are responsible for only a small percentage of cases. However, exposure to environmental toxicants is associated with an increased risk for PD in several epidemiological studies. A potential role for gene–environment interaction is claimed to explain PD etiology.
Imaging
Imaging is not informative, apart from SPECT with DaT scan that may contribute to differential diagnosis in selected cases.
28.4 Top Differential Diagnosis
Essential tremor; Parkinsonisms; vascular, toxic, and drug-induced parkinsonism; normal pressure hydrocephalus
28.5 Therapy
After 50 years from its introduction, levodopa is still the golden standard therapy in PD treatment, simply because it is the best physiological substitute for the lacking substance. The association between levodopa and dopamine-agonists may add efficacy and reduce side effects of both. IMAO-B and I-COMT have an ancillary role (e.g., in enhancing levodopa efficacy). Interventional therapies are indicated in the advanced phase of the disease.
28.6 Prognosis
General surveys demonstrated that about 30 % of patients affected by Parkinson would lose their jobs within 1 year, and most after 5 years of disease. Moreover, the annual risk of hospitalization of Parkinson was more than 30 % [1], and PD patients had a greater risk of death than those without PD [2].
Clinical worsening of PD could be the result of two distinct processes:
1.
The progression of levodopa-responsive symptoms, are associated with the degeneration of the nigrostriatal dopaminergic neurons. In PD, the age at onset of this process and its rate of progression are highly variable.
2.
The evolution of levodopa-nonresponsive symptoms (the so-called axial symptoms: gait, balance, dysarthria, dysphagia), which are caused by widespread degeneration of extranigrostriatal systems: these symptoms have a more homogeneous rate of progression and precede death by 3 to 5 years [3].
Apart from different pathological entities, which may be clustered under the definition of parkinsonisms (MSA, PSP, CBD, LBD), a wide range of phenotypic subtypes that differ in clinical features, response to therapy, prognosis, and pathology, characterizes PD. Consequently, the analysis of PD prognosis must include this clinical heterogeneity.
Several studies have addressed this issue, but only a qualitative synthesis of the prognostic factors is possible because formal meta-analysis to aggregate quantitatively progression scores of motor impairment, disability, and quality of life (QoL) is hampered by the wide variety of outcome measures used and heterogeneity of study population.
28.6.1 Genetic Factors
Genetically determined forms of PD are characterized by a wide clinical variation even among members of the same family. However, it is possible to indicate some general trends. Homozygous or compound heterozygous mutations in three genes (parkin, PINK1, DJ-1) can cause autosomal recessive forms of early-onset parkinsonism with a slower and more benign course and usually without atypical signs nor cognitive involvement. In the autosomal dominant forms there is a wider variability of the clinical course: patients with alpha-synuclein mutation (in particular the missense mutations) have a more severe course; patients carrying the LRKK2 mutations present with a clinical heterogeneity, and those with the most common mutation (G2019S) show a typical course which resembles the classical form. Parkinsonism associated with the GBA mutation is characterized by cognitive comorbidity or a typical Lewy body dementia [4].
28.6.2 Gender
28.6.3 Clinical Factors
Age at Onset
The increment of motor impairment seems to be greater in patients with older age at onset (≥78 years) after comparable disease duration of approximately 5 years [7]. A similar observation confirmed that patients with an older age at onset (>57 years) had a more rapid progression in freezing and in parts I and II of UPDRS (mentation and activities of daily living). Older age at onset has been associated with a higher worsening in UPDRS-ME and Hoehn & Yahr scales, as well as, in an incident study, with worse progression of motor impairment, disability, and quality of life [5].
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