21st June 2023

Other causes of Parkinsonism

Drug-induced Parkinsonism

Drugs that block dopamine receptors and dopamine transmission can cause secondary drug-induced parkinsonism (DIP). The decrease in dopamine causes a denervation of the D1 and D2 receptors in the nigrostriatal pathway.

The dopamine antagonists that can cause DIP are:

Antipsychotics such as fluphenazine, haloperidol, paliperidone, and risperidone
Dopaminergic anti-emetics – such as metoclopramide, domperidone, and prochlorperazine
Sodium valproate

The main difference in the presentation of DIP vs PD is the symmetrical and generalised tremor, rigidity and bradykinesia seen in DIP.

The most ideal treatment is to stop the causative drug. For psychiatric conditions, this might not be possible. In this case, the treatment for DIP is as follows:

First line – anticholinergics – benztropine and trihexyphenidyl.
Second line – amantadine.

Vascular Parkinsonism

Vascular parkinsonism (VP) is due to microangiopathy and lacunar infarcts affecting the basal ganglia, thalamus or the putaminal-pallido outflow.

Patients with VP present with:

Parkinsonian-ataxic wide-based gait
Dysphagia
Dysarthria
Hypertonia, brisk reflexes, and extensor plantar reflexes

MRI head can show white matter and periventricular hyperdensities.

The treatment for VP is levodopa for parkinsonism and antiplatelets for secondary prevention.

Chronic Traumatic Encephalopathy

Chronic traumatic encephalopathy (CTE) occurs as a result of repetitive head trauma, usually from repetitive subconcussive blows and repetitive concussions. It commonly affects professional athletes in contact sports but also ex-soldiers and domestic violence victims. This trauma causes accumulation of tau and periventricular astrocytic tangles.
Much later in life, those affected develop CTE, which presents as a mixture of parkinsonism and dementia. Unfortunately, CTE can only be definitively diagnosed at post-mortem. There is currently no specific treatment for CTE. However, preventing head trauma with protective equipment and treating traumatic brain injury well might help prevent CTE.

Toxin-induced Parkinsonism

Toxin-induced parkinsonism (TIP) is caused by prolonged exposure to certain toxins that damage dopaminergic neurons. This presents as cogwheel rigidity, bradykinesia and falling when walking backwards.

Causative toxins are:

Manganese
Copper
Mercury
MPTP – by-product of incorrectly made synthetic heroin

Wilson’s Disease

Wilson’s disease (WD) is an autosomal recessive disorder of copper metabolism from a lack of caeruloplasmin. Caeruloplasmin is the transporter protein of copper and removes excess copper. WD causes an accumulation of copper, especially in the liver and CNS.

The symptoms of WD are: