Parkinsonism can follow exposure to drugs with an antagonistic effect at D₂ receptors. This is the most common cause of secondary parkinsonism and is typically seen in patients requiring antipsychotic (neuroleptics, major tranquillizers) treatment. Newer, ‘atypical’ neuroleptics with less affinity to the D₂ receptor are less likely to result in extrapyramidal side-effects and are preferred when treating psychosis in IPD. The commonly used anti-emetic drugs metaclopramide and prochlorperazine also have a D₂ antagonist effect. Other drugs known to induce parkinsonism include lithium, tetrabenazine, reserpine, valproate, and the calcium channel blockers, cinnarizine and flunarizine.

Drug withdrawal typically results in a slow improvement although latent parkinsonism may have been unmasked and full recovery may not occur.

This is also known as ‘lower body parkinsonism’ due to prominent gait disturbance and relatively less arm involvement. Often, these patients will have early freezing which is not typically seen in IPD. This is an important cause of parkinsonism in older patients and those with a history of vascular risk factors (particularly hypertension). The pathophysiology is related to small vessel disease with prominent periventricular ischemia. Patients with basal ganglia infarcts are more likely to respond to levodopa. Magnetic resonance imaging (MRI) of brain is useful to identify those patients who may have a vascular cause of parkinsonism. Other clinical features that can help differentiate vascular from idiopathic parkinsonism are a postural more than resting tremor and preserved olfaction.

The pre-mutation state of Fragile X can present with tremor, parkinsonism and autonomic features and may therefore be misdiagnosed as essential tremor, IPD or MSA. An accurate family history is vital, looking for a history of a related child with learning disability or autism. The presence of ataxia is another important clue. In one series of 26 patients with premutations of the FMR1 gene, 57 % of cases had mild bradykinesia, resting tremor was present in 40 % and 71 % had upper limb rigidity.

Secondary parkinsonism can also occur following toxin exposure, including manganese (miners, intravenous drug abuse), carbon disulphide and 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (described by Langston JW and Palfreman J in “The Case of the Frozen Addicts”).

Rarely parkinsonism can arise as a consequence of strategically-placed structural lesions such as large Virchow-Robin (perivascular) spaces or central nervous system (CNS) tumors, more commonly supratentorial meningiomas causing basal ganglia compression than by direct tumor infiltration.

Functional parkinsonism is well recognized but rare. Clues to the diagnosis are a history of previous psychogenic illness, an abrupt onset, entrainment of tremor, selective disability and distractibility.

Essential tremor (ET) is one of the most common disorders mistaken for IPD, characterized by a postural and kinetic tremor without rest tremor. Patients with ET can have cog-wheeling but without rigidity. Where there is a combination of a resting hand tremor with essential tremor, the physician should consider rest tremor appearing late in ET, or the combined resting-postural tremor syndrome.

Parkinsonism and essential tremor could also represent the co-occurrence of two common movement disorders.

Dystonic tremor usually occurs in a dystonic body part. Some distinguish this from ‘dystonia with tremor’, tremor observed in an unaffected body part with dystonia elsewhere. Dystonic upper limb tremor will sometimes have a ‘null-point’ where rotation of the affected limb will reach a point where the tremor is abolished. Like ET, dystonic tremor of the upper limbs will not have the latent period before re-emerging on changing position as seen in IPD (re-emergent tremor). Dystonic tremor tends to be more irregular and jerky in character and may have a torsional component.

Normal pressure hydrocephalus (NPH) presents with one or all features of a triad of gait apraxia, urinary incontinence and cognitive impairment. Gait can be similar to that of vascular parkinsonism because of involvement of periventricular descending corticospinal tracts. Imaging is essential in demonstrating dilatation of all ventricles out of proportion to the degree of cortical atrophy. Diagnosis is made most reliably by removal of a large volume (at least 40 ml) of cerebral spinal fluid (CSF) via lumbar puncture, which can also predict the potential for improvement with shunt placement although this remains controversial. Video of gait and cognitive assessment performed pre and post lumbar puncture is useful for later assessment.

Rest tremor, typically of 4–5 Hz, is the first symptom recognized in 70 % of patients, but may be absent in 20 %. The classic “pill-rolling” tremor involves the thumb and forefinger and is best seen when the patient is walking. Rest tremor disappears with action but re-emerges after a latent period of seconds as the limbs maintain a posture (re–emergent tremor). Tremor increases with walking (a possible early sign), stress or excitement. Tremor is also common in the lips, chin, and tongue but not the head.

Bradykinesia encompasses slowness of movement, difficulty initiating movement and loss of automatic movement. Decrement refers to a reduction in amplitude of movement, particularly with repetitive movements. Often different tactics need to be used by the examiner to bring out bradykinesia that might only be seen during certain actions, such as finger tapping, pronation-suppination movements or opening and closing the fists. The face loses spontaneous expression (hypomimia) with decreased frequency of blinking. Speech becomes soft (hypophonia), and the voice has a monotonous tone with a lack of inflection (aprosody). Some patients do not enunciate clearly (dysarthria) and do not separate syllables clearly, thus running the words together (tachyphemia) and others stutter (palilalia). Bradykinesia of the dominant hand results in small and slow handwriting (micrographia). Difficulty rising from a deep chair, getting out of cars and turning in bed are symptoms of truncal bradykinesia. Subtle signs of bradykinesia can be detected by examining for slowness in shrugging the shoulders, smiling, lack of natural gesturing in conversation and decreased blink frequency. Walking is slow, with a shortened stride length and a tendency to shuffle with decreased heel strike; arm swing decreases and eventually is lost.

Rigidity is an increase of muscle tone on passive movement and is not velocity dependent as seen with spasticity. Resistance is equal in all directions and usually has a ‘cogwheeling’ character caused by the underlying tremor even if not visible. Rigidity of the passive limb increases while another limb is engaged in voluntary active movement, also known as the co-activation or facilitation test. Axial rigidity at the neck can similarly be accentuated by asking the patient to open and close both hands. Mild upper limb rigidity can be elicited by standing behind the patient and rocking their shoulders back and forward to produce passive arm swing that will be reduced on the more affected side.

This commonly begins in the elbows and spreads to involve the entire body. The head is bowed, the trunk is bent forward, the back is kyphotic and the arms are held in front of the body with the elbows, hips, and knees flexed. Walking is marked by festination, whereby the patient walks faster and faster with short steps, trying to move the feet forward to be under the flexed body’s center of gravity to prevent falling. Deformities of the hands include ulnar deviation, flexion of the metacarpophalangeal joints, and extension of the interphalangeal joints (striatal hand). The hallux may be dorsiflexed (striatal toe). Lateral tilting of the trunk can develop (Pisa syndrome) and extreme flexion of the trunk (camptocormia) is sometimes seen which should be abolished when lying flat.

This manifests as the transient inability to perform active movements. Freezing occurs suddenly and is transient, usually lasting seconds. It will typically occur when the patient begins to walk (start hesitation), attempts to turn while walking, approaches a destination, such as a chair in which to sit (destination hesitation). Tight spaces can also provoke freezing, such as doorways, as can time-restricted activities such as crossing heavily trafficked streets or answering the phone. The combination of freezing and loss of postural reflexes is particularly devastating, and a common cause of falls.

Constipation is almost universal in PD and can influence the efficacy of oral therapies by causing erratic absorption. Treatment with a regular stool softener, sometimes combined with a stimulant laxative is usually effective and most patients will require a regular laxative. The use of abdominal plain films can guide the use of laxatives and should be considered in patients whose motor control has deteriorated or where response to levodopa is variable.

Dysphagia is not uncommon. Rarely recurrent aspiration pneumonia can complicate late stages of the disease. Patients benefit from access to a speech and language therapist to teach strategies to improve swallowing. Dysphagia is not typically levodopa-responsive and can deteriorate after deep brain stimulation. A dry oropharyngeal mucous membrane due to anticholinergic agents is one readily treatable cause of swallowing impairment.

This is a manifestation of reduced swallow frequency in IPD as opposed to excessive saliva production. Anticholinergics are effective, but most available agents are tertiary amines that enter the CNS and can impair memory or cause hallucinations in older patients. Quaternary amines do not penetrate the CNS and are preferable. Sublingual 1 % atropine can be used with some success. Injections of botulinum toxin into the salivary glands can be attempted. Pharyngeal weakness due to local toxin diffusion is a potential complication but is rarely encountered with dry mouth being a more common side-effect.

Orthostatic hypotension (OH) can cause significant morbidity and contributes to the risk of falling. Conservative measures such as increased fluid in-take, additional dietary salt, avoidance of hot baths and large meals and the use of compression stockings can help. More resistant symptoms can respond to the sympathomimetic midodrine, starting with 5 mg and titrating up to three doses of 10 mg a day if necessary. Fludrocortisone can be used, typically starting at 0.1 mg/day but supine hypertension can result from increased salt and mineralcorticoid ingestion. Elevation of the top of the bed to 30° at night may help by reducing renal mineralcorticoid production. OH can be aggravated by dopaminergic therapy (dopamine agonists in particular), dehydration and constipation.

Detrusor hyperreflexia predominates in IPD causing frequency, urge, nocturia and sometimes incontinence. In older male patients the picture may be mixed with prostatism and anticholinergics are ideally prescribed after bladder ultrasound to determine post void residual volume, avoiding exacerbation of pre-existing outflow obstruction. Equally important is the propensity of these agents to cause cognitive impairment in older patients with IPD, in particular the tertiary amines that cross the blood–brain barrier.

Trospium chloride is a quaternary amine that may have a better side effect profile although there is little trial data available addressing this issue. Reduction in late night fluid intake can help nocturia. In patients treated for OH nocturia can occur as a result of nocturnal pressure natriuresis secondary to supine hypertension.

Sexual dysfunction is more commonly encountered in IPD than in the general population. Men with erectile dysfunction can be treated with agents such as sildenafil, however this can exacerbate OH. Female patients may report reduced libido and conversely hypersexuality can occur with dopamine agonist treatment and is particularly troublesome if associated with an impulse control disorder (discussed later).

Pain is not uncommon and can vary from uncomfortable paraesthesias to nonciceptive or neuropathic sounding pain. Patients can initially present with pain in a joint on the symptomatic side, typically a shoulder, probably due to hypokinesis and immobility. Adequate treatment and physiotherapy can improve this considerably. Some patients complain of pain down one side of their body or in an apparently radicular distribution, both of which will respond to levodopa suggesting a central dopamine deficit as the underlying cause. True radiculopathies from nerve root compression can also worsen in the ‘off’ state. Restless legs syndrome can be seen in association with IPD and can give rise to an aching discomfort in the legs at night that can improve with a low dose of a dopamine agonist taken at night.

The pathophysiology of abnormal sweating in IPD is unclear but Lewy body pathology involving the hypothalamus may be contributory. Sympathetic cholinergic fibers are the final common pathway that mediate the sweating response although dopamine would appear to play a role, as excessive sweating of the head and upper body can occur as an ‘off’ phenomenon, often in bed at night. Sweating can also occur in the context of dyskinesias, but is usually less prominent than the paroxysmal attacks of drenching sweats reported in ‘off’ periods. Other causes of excessive nocturnal sweating should be considered including thyrotoxicosis and latent tuberculosis infection.