INTRODUCTION
Parkinson's disease is characterized by tremor at rest, bradykinesia, rigidity, loss of postural reflexes, and gait problems. James Parkinson was accredited for his original well-recorded description of Parkinson's disease which is still quite correct despite advancement of understanding over the last two centuries. The historical aspects are well-discussed in chapter, “History of Parkinson's Disease: From Ancient Times to James Parkinson and Beyond”.
Parkinson's disease is not just a clinical syndrome but a pathological diagnosis that links the clinical symptoms and signs to the characteristic pathological findings on brain autopsy showing loss of pigmented dopaminergic neurons in the substantia nigra. The term “Parkinsonism” is used to describe the clinical syndrome that has close resemblance to the hallmarks of Parkinson's disease like bradykinesia, rigidity, and postural instability but have different underlying disease pathology. The etiology 2of parkinsonism can be neurodegenerative as in Parkinson's disease or atypical Parkinsonism (also called Parkinson plus syndromes) or may be a result of strokes (vascular parkinsonism), drugs (such as haloperidol or valproate), infections or encephalitis (postencephalitic), etc. (Flowchart 1 and Box 1). Parkinsonism can sometimes be an additional or even presenting clinical feature in other movement disorders such as Huntington's disease, spinocerebellar ataxias, dystonia Parkinsonism. Parkinsonian features may also be seen in metabolic defects that manifest with multiple neurological features and movement disorders (e.g., Wilson's disease, neurodegeneration with brain iron accumulation, etc).
Typically, Parkinson's disease responds well to medical therapy with dopaminergic drugs, at least in early years after diagnosis. However, the atypical Parkinsonism like multiple system atrophy (MSA) (see chapter on multiple system atrophy), progressive supranuclear palsy (PSP) (see chapter on clinical approach to progressive supranuclear palsy), dementia with Lewy bodies (DLB) (see chapter on dementia with lewy body disease), and corticobasal degeneration (CBD) (see chapter on corticobasal degeneration), have limited or no response to standard dopaminergic therapy, that is usually quite effective in Parkinson's disease. The patients with atypical Parkinsonian disorders have very limited survival and have very poor quality of life after diagnosis, and the management mainly relies on rehabilitative strategies.
FLOWCHART 1: What is and what is not Parkinson's diseaseNBIA, neurodegeneration with brain iron accumulation; SCA, spinocerebellar ataxia.
The pathologies in degenerative Parkinsonism are classified into synucleinopathies and tauopathies depending on the underlying protein abnormality in either the α-synuclein or tau (summarized in table 1). The pathophysiological features of Parkinson's disease are further discussed in “Pathophysiology and genetics of Parkinson's Disease”. Not all atypical Parkinsonism are easy to diagnose. In fact, understanding of genetically determined conditions such as fragile X ataxia tremor syndrome and other atypical, atypical Parkinsonism is useful to get to the correct diagnosis in difficult clinical situations. These conditions are discussed in “Atypical Atypical Parkinsonism”.
HISTORY AND PRESENTING COMPLAINTS
Impairments in Physical Functions
Bradykinesia or slowness of movement is the hallmark of Parkinson's disease. The fluency, coordination, efficiency, and speed of composite, and fine motor movements are usually diminished early in the disease course. This may manifest as difficulty with doing buttons, shoe laces, putting on a bra, or jewelry hooks. Sometimes, the signs appear earlier if a person's occupation or hobbies require manual dexterity and speed like catching a ball. A dancer may fail to keep up with the beat, a pianist or a musician may slow down the tempo, or a typist may get slower with the tasks. Difficulty due to slowness in getting in and out of a car or slowness when standing up after prolonged sitting on floor for prayers or assemblies may be a very early sign.
The resting tremor of Parkinson's disease is usually a slow tremor which is brought on at rest or with mental distraction (like when watching television or walking). Tremor usually is easy to detect, but often patients tend to ignore it, specifically if the tremor is at rest. In the early stages, tremor may be easy to suppress by simply moving the hand. The patients also tend to hide the tremor while walking by putting the hand in the pocket.
If the tremor is mainly postural, the symptoms may be more distressing. The patients may have difficulty using knife and forks. Spilling peas while eating, spilling a drink while pouring, and often asking for help at dinner table is common. Parkinson's disease patients with tremor additionally lack manual dexterity which makes fine hand movements almost impossible. A significant postural tremor interferes with eating, dressing, grooming, handwriting, hobbies, and tasks, and challenges the functional independence. Handwriting deteriorates commonly with 4words becoming progressively smaller as the person continues to write. While taking history, it is worth knowing the side dominance and handedness, as one generally relies on one hand more than the other for most tasks.
A combination of tremor, bradykinesia, and loss of dexterity lead to an inability in carrying out actions requiring fine motor skills, such as handling fasteners; actions requiring larger alternating or rotating movements, such as buttering and cutting bread, washing hair, and brushing teeth; and actions requiring balance, such as clothing the lower part of the body and bending over or reaching to get things out of a closet or cabinet. In addition, mental and physical fatigue and reduced stamina make it difficult to sustain activities.
Gait impairment and falls are the most dreaded complications related to Parkinson's disease. The gait impairment relates to disease progression in Parkinson's disease. Very early unprovoked falls (within 1 year) should make one suspicious feature of the diagnosis of Parkinson's disease as this is an atypical feature seen in PSP. Early falls may be related to postural hypotension which may be drug induced in cases with Parkinson's disease or may reflect the underlying diagnosis of MSA.1,2
Studies examining the risk factors for falling associated with Parkinson's disease indicate that problems with stability, transfers, walking (e.g., freezing, propulsion), and orthostatic hypotension play a primary role.3 Freezing is a common problem where feet seem unable to move as if frozen to the floor. Freezing mainly occurs when starting to walk, passing through close spaces, or large open spaces, turning or performing multiple tasks while walking.4 Based on these situations, the subtypes of freezing include: start hesitation, turn hesitation, hesitation in tight quarters, destination hesitation, and open space hesitation. Freezing is a common cause of falls. This is more common when patients have difficulty performing the transfer with sufficient speed, and usually do not bring their torsos forward enough and may fall.
Camptocormia or extreme flexed, or tilted posturing of the spine can mechanically affect walking and predispose to forward falls. The basis of camptocormia is poorly understood but it seems that there is initially an increased tone which is followed by muscle wasting and weakness later. Although craniocervical dystonia, such as blepharospasm or cervical torticollis may be seen with Parkinson's disease, anterocollis or forward flexion of neck is more suggestive of MSA.
Independent living in patients with Parkinsonism is challenged mainly by gait and balance impairment but tremor, bradykinesia (slowness of movement), dystonia, and dyskinesia (dopamine treatment induced) can also be very limiting.5 The drug-induced dyskinesia is generally choreiform. Dyskinesias are the most common long-term complication in Parkinson's disease and can be seen in almost half of all the patients after 10 years of treatment. The dyskinesia can affect speech, swallowing, posture, and gait.
Dystonia can manifest with abnormal postures which are mobile (neither are these postures fixed nor are they like contractures) and vary from time to time based on action (action dystonia) or task (task specific dystonia). Dystonia can be seen in Parkinson's disease in many forms. Blepharospasm manifests with increased blinking and closed eyes which are difficult to open spontaneously. If severe, this can lead to partial blindness. Foot dystonia is much more common in the early morning. Foot dystonia may become prominent on walking specially in off periods of 5Parkinson's disease when the medication is wearing off. Hand dystonia can present as a permanently closed hand which can be opened passively (unlike contractures). This posturing impairs the hygiene of the hands and can lead to multiple skin infections of the creases of the palm. In general, patients with Parkinson's disease get dystonia in off periods and dyskinesia as a peak dose effect with dopamine, but this is not a rule. Persistent and severe dystonia in one hand with or without an alien limb phenomenon should alert the physician to the possibility of CBD.
Impairments in Mental Functions
The pathophysiology of parkinsonism is quite complex and affects the performance of complex, well-learned movements, as well as executive function.6 This interferes with most activities of daily living that involve automatic or subconscious preplanning, initiation, and sequencing of movements. Early cognitive impairment with dementia, autonomic involvement, and hallucinations must alert one to the possibility of Lewy body dementia or DLB (see chapter on dementia with lewy body disease). Significant aphasia or apraxia can reflect cortical dysfunction which can be seen in CBD (see chapter corticobasal degeneration). Frontal executive dysfunction and disinhibition are commonly seen in PSP. There are several signs of PSP that are linked to this frontal subcortical involvement (see chapter clinical approach to progressive supranuclear palsy) like the applause sign.
Nonmotor Impairments
Sometimes, nonmotor features including anxiety, depression, psychosis (hallucinations), nocturia, constipation, and sleep problems can have a greater bearing on the quality of life than motor symptoms.
- Sensory symptoms: Anosmia and pain can be important non-motor symptoms. There can be several types of pain associated with Parkinson's disease (musculoskeletal, dystonic, radicular, central, and akathisia) and it is important to discern the root cause to offer effective intervention
- Speech and swallowing may also be affected, particularly as the condition progresses.7 Communication is less supported by nonverbal expression and gestures. Writing is affected by progressive micrographia.8 Taste may be affected and loss of smell is an early sign of Parkinson's disease. These factors may contribute to disinterest in food and weight loss
- Drooling or sialorrhoea can be very embarrassing and precludes a large amount of social interaction and contributes to social segregation in patients with Parkinson's disease. Drooling in Parkinson's disease is largely the result of swallowing difficulties rather than excessive saliva production. Although management strategies are often focussed on reducing saliva production (see chapter on nonmotor symptoms management)
- Sleep is commonly affected and rapid eye movement sleep behavior disorder may be the first sign of Parkinson's disease. Excessive daytime sleepiness is common and often due to treatable causes like obstructive sleep apnea syndrome or a side effect of medication. Other nocturnal disturbances include difficulty in turning in bed, vivid dreams, motor fluctuations, and nocturia6
- Breathing difficulties are uncommon apart from obstructive sleep apnea, but if inspiratory sigh or stridor is present, MSA should be considered
- Neuropsychiatric features include dopamine dysregulation syndrome, commonly due to dopamine agonists and dopamine dependence. Hallucinations may be a sign of drug induced psychosis, or DLB.
As indicated in flowchart 2, specific features may occur with individual varieties of atypical Parkinsonism. Progressive supranuclear palsy is associated with early falls, limitation of eye movements, cognitive decline, and dysarthria9 (see chapter on PSP). Multiple system atrophy is often complicated by early and severe postural hypotension, urinary incontinence, and anterocollis of neck, dysarthria, and sometimes cerebellar ataxia10 (see chapter on multiple system atrophy). Dementia with Lewy bodies is associated with severe hallucinations, cognitive decline, bladder dysfunction, and postural hypotension (see chapter on dementia with lewy body disease). Corticobasal degeneration is complicated by concurrent myoclonus, dystonia, and apraxia of limb (see chapter on corticobasal degeneration). Alien limb phenomenon which is unique in this condition can be refractory to all current treatment strategies and with apraxia, it can make one hand entirely useless and autonomous. This phenomenon is very rare in practice.
Other Clinical Features that Help Differentials
Strokes and vascular changes can present with features similar to Parkinson's disease. Normal pressure hydrocephalus (NPH) may have gait problems similar to Parkinson's disease with cognitive impairment and urinary incontinence. One must be careful in eliciting history of vascular risk factors. Trauma and subdural hematoma (SDH) may present with Parkinsonism. Exposure to toxins and drugs must be excluded and a family history of Parkinson's disease or tremor may be useful. Some conditions may superficially resemble Parkinson's disease but have a different heredodegenerative basis like the Westphal variant of Huntington's disease, Wilson's disease, spinocerebellar ataxias with Parkinsonism, neurodegeneration with brain iron accumulation, and primary familial brain calcification. Some of these conditions are discussed elsewhere in this book.7
EXAMINING A PATIENT WITH SUSPECTED PARKINSON'S DISEASE
Gait
The gait of a patient with Parkinson's disease can be a very important sign. Usually, observing a patient walking in the clinic with a slow shuffling gait, slightly bent forward posture, and reduced arm swing with tremor in one hand is almost pictorial. One may have to observe more closely to pick up changes such as mild dystonia or dragging of one leg, or subtle features of freezing especially while passing doorways. It is always useful to observe the stride length and lift from the ground, both of which are reduced in Parkinson's disease. Festination is the tendency to walk faster with small steps, as if trying to catch the center of gravity to prevent a fall. Freezing commonly presents with the feet being stuck to the floor. It is slightly different and more prolonged than start hesitation and can happen when approaching narrow paths or when the landscape of the road or path is changing. Standing behind the patient and giving them a gentle tug backwards to displace their balance can be a good test (called pull test) for postural instability. Normally a person should be able to resist the pull or take up to 2 corrective steps backwards, but a patient with Parkinsonism will tend to fall or take more than 2 steps. Postural instability might be earlier in onset in atypical Parkinsonism such as PSP where falls and postural instability can appear within the first year.
Tremor
The best way to examine a patient for resting tremor is asking them to sit with their hands completely relaxed in their lap (distracting them with conversation can help) or while walking. If the tremor has the classic pill rolling character (as if rolling a pill or a rosary bead between the finger and thumb), it is almost diagnostic of Parkinson's disease. The commonest differential for Parkinson's disease tremor are essential tremor and dystonic tremor.11
Postural tremor can be seen in Parkinson's disease but there is often a slight pause after moving the hand from a resting state with tremor, before the tremor re-emerges as a postural tremor. This re-emergent tremor is almost characteristic of Parkinson's disease.
The other features that distinguish the different varieties of tremors are listed in table 2. The cerebellar tremors usually have past pointing and dysdiadochokinesia. The functional tremor can be very difficult to distinguish and there can be a presentation that mimics functional Parkinsonism. Specifically, the tremor is very variable and can vary in being side to side at sometimes and up and down on others. The amplitude can also vary. These tremors are distractible and get better when the patient is asked to do some mental tasks like arithmetic or physical tasks such as alternating finger movements with the other hand. It may be possible to train the frequency of functional tremor by tapping one hand at a certain speed the tremor takes on the speed of the taps. These phenomenon, variability, distraction, and entrainability help with the diagnosis of functional tremor.12 It is worth noting that patients with atypical Parkinsonism such as PSP and corticobasal syndrome do not 8have the rest tremor, however, MSA and DLB can look very similar to Parkinson's disease with respect to the tremor in the early stages. Myoclonus with tremor can be seen in MSA.
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Bradykinesia
Finger and foot taps are the most crucial part of examination of a patient with suspected Parkinson's disease. There is slowness with a decremental response that helps identify “true” bradykinesia. Whole body bradykinesia may be identified by reduced overall movements and some other signs include drooling (due to bradykinesia of swallow) and reduced blink rate. False bradykinesia can be seen with corticospinal involvement which is associated with weakness and corticospinal features.9
Rigidity
The rigidity of Parkinsonism is best appreciated distally at wrist and elbow with slow movements (contrary to fast velocity for spasticity). The classic cogwheel rigidity is commonly asymmetric with it being more on one side. Striatal extension of toe is a useful sign of Parkinsonism. Axial rigidity may be more than limb rigidity in atypical Parkinsonism and akinetic rigid variety of Parkinson's disease.
Ocular Features
Eye movements should be normal on bedside examination in Parkinson's disease and MSA. Supranuclear gaze palsy can be seen in PSP and tested by looking for saccades, pursuit, and range of movement. The saccades are slow, pursuits are broken, and vertical gaze restriction is seen in PSP. Corticobasal syndrome may have slow initiation of saccades with mild restriction of gaze.
Dysarthria and Lower Cranial Nerves
Parkinson's disease patients characteristically have dysarthria with decreased volume, slow articulation, faster or slower speech rate and a monotone, high pitch voice.13 Growling dysarthria is seen in PSP and low volume quivery dysarthria has been described in MSA.14 Swallowing may be impaired in Parkinson's disease but early involvement of swallowing due to pseudobulbar palsy is seen in patients with PSP.
Table 3 summarizes the essentials of neurological examination in a patient with suspected Parkinson's disease.
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Neurological Examination
Corticospinal features are not expected in a case with Parkinson's disease and if present one must look for evidence of strokes, cervical myelopathy, subdural hematoma, or suspect MSA. Similarly, presence of cerebellar signs should alert one for the possibility of MSA or stroke.
Diagnosing Parkinson's Disease
The diagnostic criteria for Parkinson's disease are derived from a large pathological series15 but the rate of diagnosis can vary. The National Institute of Neurological Disorders and Stroke diagnostic criteria are included in Box 2 and UK Parkinson's Disease Brain Bank criteria in flowchart 3.
There are several rating scales used in assessment of Parkinson's disease.16 The appendix contains the Movement Disorder Society Unified Parkinson's Disease Rating Scale and Non-Motor Scale questionnaire, the most accepted questionnaires used in assessment.
Differential Diagnosis of Parkinsonism
Table 4 summarizes the clinical features in Parkinsonism.
INVESTIGATIONS
Usually the blood tests, and brain imaging are normal in Parkinson's disease. There is a strong argument that the diagnosis is purely clinical and sometimes in clinical settings one can avoid any investigations and start treatment for the patient with Parkinson's disease. However, some clinical scenarios require excluding other causes. Blood tests are helpful to exclude Wilson's disease and in people less than 50 years, urinary copper and serum caeruloplasmin are indicated. Computed tomography scan or magnetic resonance imaging of brain can help exclude NPH, SDH, Stroke affecting the basal ganglia, and other lesions that can present with Parkinson's disease like presentation. Neuroimaging can also help identify calcium, iron, or manganese deposition that can be linked to Parkinsonism. In atypical Parkinsonism, characteristic midbrain atrophy in PSP or hot cross bun sign in MSA are almost diagnostic. Posterior rim of iron in putamen can help diagnose MSA. Face of giant Panda in Wilsons’ or caudate atrophy in Huntington disease can also suggest alternative diagnosis.
Nuclear imaging with DaTscan can be very helpful when distinguishing Parkinson's disease from other causes of tremor. Metaiodobenzylguanidine scan is specifically abnormal in Parkinson's disease and can help differentiate Parkinson's disease from atypical parkinsonism. Details of neuroimaging are discussed in chapter “Nuclear imaging in Parkinsonism”12
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CONCLUSION
Parkinsonism is characterized by bradykinesia, with additional features of tremor, postural instability, and rigidity. The diagnosis of Parkinson's disease is clinical and a typical patient with early Parkinson's disease may have asymmetric bradykinesia, rest tremor, and cogwheel rigidity with mild postural imbalance. A careful history and examination, standardized diagnostic criteria, and monitoring scales at the initial and each follow-up visit can help manage nonmotor features, monitor progression and response to treatment, and help identify unusual features to suggest atypical parkinsonism or an alternative diagnosis. Investigations are not always needed but can be supportive of a clinical diagnosis of Parkinson's disease.
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