Parkinson's Disease: Chameleons and Mimics
The distinctive pathological features of PD have led to robust and well-validated clinical diagnostic criteria. In 1988, Gibb and Lees developed the Queen Square Brain Bank (QSBB) criteria for PD, based on careful clinical observation combined with clinicopathological correlation. In 1992, Hughes and colleagues showed that only 76% of patients diagnosed as having PD by UK neurologists fulfilled the neuropathological diagnostic criteria for the disease. Retrospective application of the QSBB clinical criteria improved the diagnostic accuracy to 82%. Multiple system atrophy, progressive supranuclear palsy, Alzheimer's disease, Alzheimer-like pathology and vascular parkinsonism comprised most of the alternative diagnoses. The same group's subsequent study in 2001 showed that the clinical diagnosis accuracy had improved to 90%. The QSBB criteria remain a benchmark for PD diagnosis, and careful application and appreciation of the criteria will prevent most pitfalls for the clinician. However, it is important to appreciate that many patients with PD may not fulfil the QSBB criteria for PD at presentation (Box 1). Expert clinicians are reportedly more accurate than the QSBB criteria at diagnosing PD, and this presumably relates to the integration of a number of sometimes subtle historical and examination findings. Parkinson's syndrome (stage 1 of the QSBB criteria) is defined by bradykinesia and one additional feature of tremor, rigidity or postural instability. Bradykinesia can be appreciated as a general slowness and paucity of movement, particularly in a decrease in the normal spontaneous fidgeting and gestural movements that occur during the interview. Parkinsonian bradykinesia is specifically elicited by examining repeated movements, usually finger taps, hand grips, pronation–supination movements, toe taps and heel stamps, following the scheme of the Movement Disorders Society unified PD rating scale (MDS-UPDRS). In PD, there is a specific form of bradykinesia involving progressive loss of the speed and amplitude of repetitive movements and there may be arrests in movements and 're-setting'. There is also a perceptible slowness of initiation and subtle weakness. The MDS-UPDRS scheme mandates that these movements are assessed over 10 repetitions. Many other factors can affect the ability to carry out repeated movements, including arthritis, pyramidal deficits, dyspraxia, depression, obsessional slowness, cerebellar disease, dystonia and other cognitive deficits. These concurrent comorbidities may make identification of true bradykinesia difficult in some patients, particularly the elderly. It is important that parkinsonian bradykinesia is not 'over-diagnosed' and these PD–bradykinesia mimics are a potential pitfall for the unwary. Bradykinesia can be difficult to assess in patients with marked postural tremor. If there is uncertainty as to whether there is genuine parkinsonian bradykinesia, we refer to the abnormality of movement as 'clumsiness' or of 'slowness of movement without decrement', pending further diagnostic information. A history of fatigable movement ('I can start brushing my teeth normally but then the movements fade out'), the presence of generalised bradykinesia and the ability to assess multiple movements (ie, arms and legs) as outlined above can help in assessing ambiguous cases.
It is important to appreciate that fulfilling stage 1 criteria is not equivalent to fulfilling the QSBB diagnostic criteria for PD as there should be no exclusion criteria, and three supportive criteria should be present (Box 1). The supportive criteria include the presence of a typical 4–6 Hz resting tremor. Patients without a typical resting tremor are unlikely to fulfil the QSBB criteria for PD at presentation, as six of the other features relate to disease course and treatment response. Resting tremor can be assessed in clinic by asking the patient to relax in a chair with arms supported and asking them to carry out a distraction task, such as counting backwards or lying on the couch in a relaxed position. In PD, the tremor normally stops on starting a movement but may re-emerge with sustained posture (re-emergent tremor). PD tremor can affect the lips, chin and legs, while head and neck tremor points towards other disorders. PD is an asymmetrical disease, and asymmetry at onset and through the disease course are both important supportive criteria. Additional features that have emerged since the publication of the QSBB criteria—and that may help to support a diagnosis of PD early in the disease course—include anosmia, prodromal constipation and rapid eye movement (REM) sleep behaviour disorder. Observing the clinical course and progression of a patient with suspected PD is one of the most important aspects of making an accurate diagnosis. PD is progressive, and disability related to cognition and gait usually occurs more than 5 years after disease onset. The response to drug treatment is an important part of the assessment. Patients with PD usually respond well to levodopa, but 20%–40% of patients develop levodopa-induced dyskinesia within 5 years, although in most patients this is not disabling. In PD, particularly in patients with akinetic–rigid dominant presentations, there is usually a marked (>70%) beneficial response to levodopa treatment.
Typical PD and the Clinical Examination
The distinctive pathological features of PD have led to robust and well-validated clinical diagnostic criteria. In 1988, Gibb and Lees developed the Queen Square Brain Bank (QSBB) criteria for PD, based on careful clinical observation combined with clinicopathological correlation. In 1992, Hughes and colleagues showed that only 76% of patients diagnosed as having PD by UK neurologists fulfilled the neuropathological diagnostic criteria for the disease. Retrospective application of the QSBB clinical criteria improved the diagnostic accuracy to 82%. Multiple system atrophy, progressive supranuclear palsy, Alzheimer's disease, Alzheimer-like pathology and vascular parkinsonism comprised most of the alternative diagnoses. The same group's subsequent study in 2001 showed that the clinical diagnosis accuracy had improved to 90%. The QSBB criteria remain a benchmark for PD diagnosis, and careful application and appreciation of the criteria will prevent most pitfalls for the clinician. However, it is important to appreciate that many patients with PD may not fulfil the QSBB criteria for PD at presentation (Box 1). Expert clinicians are reportedly more accurate than the QSBB criteria at diagnosing PD, and this presumably relates to the integration of a number of sometimes subtle historical and examination findings. Parkinson's syndrome (stage 1 of the QSBB criteria) is defined by bradykinesia and one additional feature of tremor, rigidity or postural instability. Bradykinesia can be appreciated as a general slowness and paucity of movement, particularly in a decrease in the normal spontaneous fidgeting and gestural movements that occur during the interview. Parkinsonian bradykinesia is specifically elicited by examining repeated movements, usually finger taps, hand grips, pronation–supination movements, toe taps and heel stamps, following the scheme of the Movement Disorders Society unified PD rating scale (MDS-UPDRS). In PD, there is a specific form of bradykinesia involving progressive loss of the speed and amplitude of repetitive movements and there may be arrests in movements and 're-setting'. There is also a perceptible slowness of initiation and subtle weakness. The MDS-UPDRS scheme mandates that these movements are assessed over 10 repetitions. Many other factors can affect the ability to carry out repeated movements, including arthritis, pyramidal deficits, dyspraxia, depression, obsessional slowness, cerebellar disease, dystonia and other cognitive deficits. These concurrent comorbidities may make identification of true bradykinesia difficult in some patients, particularly the elderly. It is important that parkinsonian bradykinesia is not 'over-diagnosed' and these PD–bradykinesia mimics are a potential pitfall for the unwary. Bradykinesia can be difficult to assess in patients with marked postural tremor. If there is uncertainty as to whether there is genuine parkinsonian bradykinesia, we refer to the abnormality of movement as 'clumsiness' or of 'slowness of movement without decrement', pending further diagnostic information. A history of fatigable movement ('I can start brushing my teeth normally but then the movements fade out'), the presence of generalised bradykinesia and the ability to assess multiple movements (ie, arms and legs) as outlined above can help in assessing ambiguous cases.
It is important to appreciate that fulfilling stage 1 criteria is not equivalent to fulfilling the QSBB diagnostic criteria for PD as there should be no exclusion criteria, and three supportive criteria should be present (Box 1). The supportive criteria include the presence of a typical 4–6 Hz resting tremor. Patients without a typical resting tremor are unlikely to fulfil the QSBB criteria for PD at presentation, as six of the other features relate to disease course and treatment response. Resting tremor can be assessed in clinic by asking the patient to relax in a chair with arms supported and asking them to carry out a distraction task, such as counting backwards or lying on the couch in a relaxed position. In PD, the tremor normally stops on starting a movement but may re-emerge with sustained posture (re-emergent tremor). PD tremor can affect the lips, chin and legs, while head and neck tremor points towards other disorders. PD is an asymmetrical disease, and asymmetry at onset and through the disease course are both important supportive criteria. Additional features that have emerged since the publication of the QSBB criteria—and that may help to support a diagnosis of PD early in the disease course—include anosmia, prodromal constipation and rapid eye movement (REM) sleep behaviour disorder. Observing the clinical course and progression of a patient with suspected PD is one of the most important aspects of making an accurate diagnosis. PD is progressive, and disability related to cognition and gait usually occurs more than 5 years after disease onset. The response to drug treatment is an important part of the assessment. Patients with PD usually respond well to levodopa, but 20%–40% of patients develop levodopa-induced dyskinesia within 5 years, although in most patients this is not disabling. In PD, particularly in patients with akinetic–rigid dominant presentations, there is usually a marked (>70%) beneficial response to levodopa treatment.
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