Because of dramatic heterogeneity in the expression of these cardinal motor features in IPD, patients are often subcategorized based upon the most prominent features of their motor exam. Well-recognized motor subtypes include tremor-predominant, akinetic-rigid, postural instability gait disorder PD (PIGD), and mixed [19]. Tremor-predominant patients are those with significant tremors that overshadow the other motor features of the disease, while akinetic-rigid patients have prominent bradykinesia and rigidity with little to no tremor. PIGD patients have prominent postural and gait abnormalities, while mixed patients have roughly equal amounts of all of the cardinal motor features. Recent research has suggested that these motor subtypes differ with regard to the frequency of comorbid nonmotor features, disease prognosis, and response to certain treatments [20–22]. For example, tremor-predominant patients generally have a good prognosis with slow disease progression while PIGD patients have a poor prognosis with rapid progression, dementia, and depression [19].
Nonmotor Symptoms
Along with the classic motor features of IPD, patients often suffer from a variety of nonmotor symptoms that can sometimes precede the onset of motor symptoms by several years [23]. When nonmotor symptoms are the presenting symptoms, diagnosis is often delayed at 1.6 years versus 1.0 year for individuals with motor presentations [2]. Recognition of a nonmotor prodrome of PD has instigated a debate about whether new diagnostic criteria for early-stage and prodromal PD should be created [24]; for now, however, a diagnosis of PD still requires the motor syndrome. The spectrum of nonmotor symptoms in IPD can include olfactory dysfunction, urinary dysfunction, constipation, depression, anxiety, apathy, cognitive decline, sleep disorders such as REM (rapid eye movement) sleep behavior disorder and restless legs syndrome, fatigue and orthostatic hypotension. While many of these nonmotor symptoms are common in the general population and are certainly not specific to IPD, their presence in conjunction with early parkinsonism can help further support an IPD diagnosis.
Patients with IPD should exhibit a robust and sustained response to levodopa therapy. Over time, as the degenerative disease progresses, doses need to be increased and complications of therapy are likely to emerge, most commonly levodopa-induced dyskinesia, motor and nonmotor fluctuations [25]. The various forms of parkinsonism (discussed later) may have an initial response to levodopa therapy; however, this response is generally transient and wanes quickly despite increases in dose. Many will have no response at all.
Differential Diagnosis
The differential diagnosis for IPD most commonly includes the Parkinson-plus syndromes (dementia with Lewy bodies, multiple system atrophy, progressive supra-nuclear palsy, and corticobasal degeneration), vascular parkinsonism, drug-induced parkinsonism, dopa responsive dystonia, normal pressure hydrocephalus, and essential tremor. Each of these conditions will be discussed in further detail below.
Parkinson-Plus Syndromes
Dementia with Lewy bodies (DLB) may initially resemble IPD as it can present with parkinsonian motor signs, but the distinguishing feature of this disease is the presence of a progressive dementia with deficits in attention and executive function that occurs before or within 1 year of the development of parkinsonian motor signs [26]. This is in contrast to the dementia that can develop in IPD, which usually occurs many years into the disease course. Patients with DLB often have well-formed, visual hallucinations with this disorder. Motor parkinsonian symptoms do not improve with dopaminergic therapy and caution should be used with these patients as psychiatric symptoms may be exacerbated by even small doses of these medications [27]. Diagnostic criteria for probable DLB require the presence of dementia plus at least 2 of the following 3 core features: fluctuating attention and concentration, recurrent well-formed visual hallucinations, and spontaneous parkinsonian motor signs. Suggestive clinical features include REM behavior disorder, severe neuroleptic sensitivity, and low dopamine transporter uptake in the basal ganglia on SPECT or PET imaging. In the absence of 2 core features, the diagnosis of probable DLB can also be made if dementia plus at least 1 suggestive feature is present with just 1 core feature. Possible DLB can be diagnosed with the presence of dementia plus 1 core or suggestive feature. These criteria are 83% sensitive and 95% specific for the presence of neocortical Lewy bodies at autopsy [27]. Other supportive clinical features include repeated falls, syncope, transient loss of consciousness, severe autonomic dysfunction, depression, and systematized delusions or hallucinations in other sensory and perceptual modalities [27]. Definitive diagnosis requires pathological confirmation.