Differentials
Essential tremor
SIGNS / SYMPTOMS
Characterised by a progressive tremor of the upper extremities, present in posture and action, without other neurological signs or symptoms. Only rarely present at rest.
Asymmetry (ipsilateral arm or leg tremor), bradykinesia, and rigidity usually do not occur.
INVESTIGATIONS
Tremor frequency may aid in distinguishing from PD.
Progressive supranuclear palsy (PSP)
SIGNS / SYMPTOMS
Gaze palsies and early falls within 1 year of diagnosis.[92]
Neurological examination: vertical gaze palsy and significant postural instability.
INVESTIGATIONS
Evidence of midbrain atrophy on MRI brain can be supportive of PSP diagnosis, but is not definitive.
Multiple system atrophy (MSA; MSA-A, formerly Shy-Drager syndrome; MSA-P, striatonigral degeneration; MSA-C, olivopontocerebellar atrophy)
SIGNS / SYMPTOMS
Poor response to levodopa.
Autonomic dysfunction (symptomatic hypotension, constipation, urinary urge incontinence, faecal incontinence, urinary retention, persistent erectile dysfunction).
Speech or bulbar dysfunction.[93]
Pyramidal or cerebellar dysfunction. Neurological examination reveals deficits outside of the extrapyramidal system (i.e., pyramidal, cerebellar, or autonomic deficits).
INVESTIGATIONS
Evidence of pontine and cerebellar atrophy on MRI brain can be supportive of MSA-C diagnosis, but is not definitive.
Electromyography (EMG) may demonstrate denervation and reinnervation of rectal sphincter muscle.
Iodine-131-meta-iodobenzylguanidine (MIBG) scan may be normal, whereas in idiopathic PD abnormal result expected.
Dementia with Lewy bodies
SIGNS / SYMPTOMS
Progressive cognitive decline, hallucinations, fluctuating mental status, behavioural and sleep disorders.[94] History is often sufficient for diagnosis. PD dementia is suggested if a patient had a diagnosis of PD for at least 1 year before the onset of dementia; dementia with Lewy bodies is suggested if dementia was present at symptom onset or within 1 year of parkinsonism onset.[95]
INVESTIGATIONS
Neuropsychometric testing may distinguish domains of cognitive deficits.
Corticobasal degeneration
SIGNS / SYMPTOMS
Apraxia, alien limb phenomenon, cortical sensory loss on neurological examination.
INVESTIGATIONS
None.
Alzheimer's disease with parkinsonism
SIGNS / SYMPTOMS
Dementia, aphasia.
INVESTIGATIONS
Neuropsychometric testing.
Drug-induced parkinsonism
SIGNS / SYMPTOMS
History of antipsychotic, metoclopramide, reserpine, tetrabenazine, lithium, or calcium-channel blocker usage.
Symmetrical symptoms. History is sufficient to make diagnosis.
INVESTIGATIONS
Functional neuroimaging of striatal dopamine transporter uptake, using FP-CIT SPECT, beta-CIT SPECT, or fluorodopa PET, can be helpful in differentiating from neurodegenerative parkinsonism (i.e., scan would be normal in drug-induced parkinsonism).[79]
Metabolic abnormalities
SIGNS / SYMPTOMS
History of hypoxia, hepatocerebral degeneration, hypocalcaemia.
Symmetrical symptoms.
INVESTIGATIONS
Electrolyte testing (laboratory) will demonstrate abnormalities (i.e., liver dysfunction, hypocalcaemia).
Normal pressure hydrocephalus
SIGNS / SYMPTOMS
Dementia, incontinence, prominent gait abnormalities.
Rapid or subacute onset.
INVESTIGATIONS
CT head or MRI brain will demonstrate ventricular enlargement incongruous with degree of atrophy. MRI flow study may also demonstrate increased cerebrospinal fluid (CSF) flow velocity.
Large-volume CSF tap may lead to temporary improvement of symptoms.
Structural abnormalities
SIGNS / SYMPTOMS
History of tumour, hydrocephalus, subdural haematoma, or trauma.
INVESTIGATIONS
MRI brain shows abnormalities consistent with specific aetiology (i.e., tumour = mass; stroke = area of encephalomalacia; subdural haematoma = collection of blood).
Vascular parkinsonism
SIGNS / SYMPTOMS
Lower extremity prominence of symptoms.
Symmetrical symptoms.
Stepwise progression.
Less responsive to levodopa.
INVESTIGATIONS
MRI brain shows significant small vessel disease or basal ganglia lacunar infarct(s).
Toxin exposure
SIGNS / SYMPTOMS
History of carbon monoxide, manganese, or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) exposure.
Acute onset.
INVESTIGATIONS
MRI brain: abnormalities (T2 changes) in basal ganglia noted.
Infection
SIGNS / SYMPTOMS
History of AIDS, subacute sclerosing panencephalitis, or postencephalitic or prion disease.
Acute or subacute onset.
INVESTIGATIONS
Abnormalities on MRI brain (any changes); serologies (HIV); cerebrospinal fluid (any abnormalities).
Hereditary disorders
SIGNS / SYMPTOMS
History of Huntington's disease, spinocerebellar ataxias, Wilson's disease, neurodegeneration with brain iron accumulation (formerly Hallervorden-Spatz disease), parkinsonism-dementia-amyotrophic lateral sclerosis, and mitochondrial cytopathies.
Juvenile PD or young-onset PD.
Associated chorea, myoclonus, cerebellar dysfunction, and dementia.
Kayser-Fleischer rings on slit-lamp examination support a diagnosis of Wilson's disease.
INVESTIGATIONS
Serological genetic testing will identify mutation.
Low serum ceruloplasmin and elevated 24-hour urine copper support a diagnosis of Wilson's disease.
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