Value of combined midbrain sonography, olfactory and motor function assessment in the differential diagnosis of early Parkinson's disease.

OBJECTIVE: Characteristic features of Parkinson's disease (PD) are asymmetric parkinsonian motor signs, hyposmia and substantia nigra (SN) hyperechogenicity on transcranial ultrasound. However, each of these features has limited diagnostic value as they may be present, albeit less frequently, in other parkinsonian disorders. Here, the diagnostic sensitivity and specificity of combined assessment of these three features are evaluated. METHODS: 632 patients with parkinsonism (PD, vascular parkinsonism, atypical parkinsonian syndromes, essential tremor and major depressive disorder with motor slowing) were assessed on the Unified Parkinson's disease Rating Scale for motor asymmetry (right-left score difference ≥2), the 12 item Sniffin' Sticks test (SS-12) and transcranial ultrasound. The derivation (validation) cohort consisted of 517 (115) subjects (193 (35) women; age 65.4±9.6 (62.3±10.3) years) of whom 385 (68) had PD and 132 (47) non-PD parkinsonism; another 21 (6) subjects were not included due to missing transcranial insonability. Of the validation cohort, all patients had a disease duration ≤2 years and observers were blind to diagnoses. RESULTS: The optimum cut-off values for discrimination of PD were SS-12 score <8 (hyposmia) and SN echogenic size ≥0.24 cm(2) (SN hyperechogenicity). Sensitivity, specificity and positive predictive values for the diagnosis of PD were as follows, for the derivation cohort: motor asymmetry 88%, 54% and 85%; hyposmia 75%, 70% and 88%; SN hyperechogenicity 90%, 63% and 88%; two features present 96%, 72% and 91%; three features present 57%, 94% and 97%; and for the validation cohort: two features present 91%, 77% and 85%; three features present 49%, 98% and 97%. CONCLUSION: The combined assessment of motor asymmetry, hyposmia and SN hyperechogenicity improves diagnostic specificity and allows early diagnosis of PD.

Depression and Parkinson's disease.

Depression occurs in approximately 45% of all patients with Parkinson's disease (PD), reduces quality of life independent of motor symptoms and seems to be underrated and undertreated. Characteristics of symptoms differ from major depression. Because of overlapping clinical symptoms, diagnosis is based on subjectively experienced anhedonia and feeling of emptiness. Available rating scales for major depression may not be adequate to correctly measure severity of depression in PD. Anxiety and depression may manifest as first symptoms of PD many years before motor symptoms. Serotonergic, noradrenergic and dopaminergic mechanisms play key roles in the etiology of depression in PD. Tricyclic and newer, selective antidepressants including serotonin and noradrenaline reuptake inhibitors (SSRI, SNRI) appear to be effective in treating depression in PD. Selective reuptake inhibitors seem to have a favorable side effect profile. Recent controlled studies show antidepressant effects of pramipexole in bipolar II depression. New dopamine agonists pramipexole and ropinirole appear to ameliorate depressive symptoms in PD in addition to effects on motor symptoms. There is a lack of appropriate rating scales and controlled studies regarding depression in PD.

Dementia in idiopathic Parkinson's syndrome.

Approximately 25% of patients with idiopathic Parkinson's disease (IPD) later develop dementia, with the typical characteristics as detailed in ICD-10 and DSM-IV. Differential diagnosis has to exclude dementia due to Lewy bodies, subcortical vascular encephalopathy and subcortical dementia due to progressive supranuclear paralysis or corticobasal degeneration. Several studies showed promising results for cholinesterase inhibitors such as donepezile, rivastigmine and galantamine. The demented Parkinsonian patients then present with improvement in cognitive function while motor skills do not deteriorate.

Potential impact of self-perceived prodromal symptoms on the early diagnosis of Parkinson's disease.

The detection of Parkinson's disease (PD) at stages earlier than current diagnostic criteria allow for may increase the efficacy of disease-modifying therapies. Here we studied the relationship between retrospectively reported prodromal non-motor and motor features of PD, their pre-diagnostic presentation to physicians, and the extrapolated potential of an earlier diagnosis of PD considering early diagnostic markers detected at presence. One hundred and fifteen PD patients (41 women; age 63.2 ± 8.6 years) underwent a structured face-to-face interview on 22 prediagnostic symptoms. Present olfactory function, motor symptoms, and substantia nigra hyperechogenicity (SN-h) were assessed using standardized tools. Most frequently self-perceived symptoms in the early and very early prediagnostic phase (>2, >7 years prior to diagnosis) were hyposmia (23, 10 %), musculoskeletal pain (21, 9 %), and depression/anxiety (14, 11 %). In the late prediagnostic phase (≤ 2 years) mild motor signs, especially asymmetric bradykinesia and rest tremor, increasingly dominated the self-perception. In the prediagnostic phase, 99 % of patients consulted a physician because of motor symptoms but only 36 % with non-motor symptoms, mostly pain (20 %), depression/anxiety (9 %), constipation, bladder urgency, insomnia, REM sleep behaviour disorder, sexual dysfunction, and malignant melanoma (each, <6 %). Assuming the potential detectability of present hyposmia, asymmetric motor slowing and SN-h, a triad highly specific for PD, as early as 5 years prior to diagnosis, up to 84 (73 %) patients could have been identified in the prediagnostic phase using their or their physicians' awareness of early symptoms. We conclude that educating the general population and physicians on the importance of distinct prodromal features and applying symptom-specific diagnostic programs can improve the early detection of PD.