Next Lesson - Infections of the Central Nervous System
Core
To understand movement disorders, it is important to first get an understanding of the control centres of movement in the brain. Movement is primarily controlled by the cortico-spinal system which involves the pre-central gyrus (the fold of cerebral cortex that contains the primary motor cortex), the descending tracts, and the spinal cord. Given these descending tracts form the pyramids on the ventral aspect of the medulla (the lowest part of the brainstem), neurologists refer to conditions involving this system as pyramidal disorders. The corticospinal system, and what happens when it is damaged, is explained in much more detail in our article Motor System.
However, the motor system is much more complex than this. In addition to the cortico-spinal tract, there is the extrapyramidal motor system that helps the central nervous system modulate and refine voluntary movement. Conditions affecting this system are referred to by neurologists as extrapyramidal disorders, as their pathology occurs outside the medullary pyramids of the corticospinal tracts. This article will focus on the basal ganglia, the main part of this system, and the cerebellum, which works closely with it.
The basal ganglia are a group of nuclei deep within the brain (nuclei being a group of neuronal cell bodies). The basal ganglia communicate with the motor cortex via the thalamus, meaning increased thalamic activity increases cortical activity and vice versa.
The basal ganglia are made up of the structures listed below. Each disease later in this article damages one of them: the substantia nigra pars compacta in Parkinson’s disease, the striatum in Huntington’s disease, and the subthalamic nucleus in hemiballismus.
- Substantia Nigra Pars Compacta (SNc) - the main source of dopamine for the striatum, found in the midbrain (the upper part of the brainstem).
- Striatum - made up of two portions, and receiving inputs from the SNc and the cortex:
- Caudate Nucleus - C-shaped nucleus that forms part of the lateral wall of each lateral ventricle.
- Putamen
- Lentiform Nucleus - made up of two structures that are anatomically closely related but functionally very different (note that the putamen is also part of the striatum):
- Globus Pallidus - has an internal and external segment.
- Putamen
- Subthalamic Nucleus
The full role of the basal ganglia is still debated, so you do not need to know it in detail at this level.
One of its known effects is to fine-tune voluntary movements by reinforcing appropriate movements and inhibiting inappropriate ones. This is best visualised by thinking about a simple behaviour like kicking a ball. The direct pathway acts to facilitate appropriate actions (in this case hip flexion to bring the leg forwards). The indirect pathway acts to inhibit inappropriate actions (in this case hip extension, which would pull the leg backwards and work against the kick).
The direct and indirect pathways are modulated by dopamine, which changes how active each pathway is. Dopamine acts on two types of receptor, called D1 and D2. It binds to excitatory D1 receptors (which make a cell more likely to fire) to facilitate movement via the direct pathway, and to inhibitory D2 receptors (which make a cell less likely to fire) to inhibit the indirect pathway. Inhibiting the indirect pathway also facilitates movement at the level of the motor cortex. In turn, other components of the basal ganglia also have excitatory and inhibitory effects on one another. They use mainly glutamate as the excitatory neurotransmitter, and GABA (gamma-aminobutyric acid) as the inhibitory one.
Here is an attempt at showing the circuit in a simplified manner. You do not need to learn this in detail for medical school exams. You should, however, be able to demonstrate an understanding of inhibitory vs excitatory, and apply this knowledge in the context of pathology explained later in this article.
Diagram - The motor pathways in the brain. It shows the different excitatory and inhibitory pathways, and the different neurotransmitters
SimpleMed original by Dr. Elena Perez
Ultimately, understanding this circuit can help understand how diseases that affect components of the basal ganglia result in different presentations of pathology.
Parkinson’s disease is one of the main extrapyramidal motor disorders. It occurs as a result of degeneration of the dopaminergic neurones (nerve cells that make dopamine) in the substantia nigra pars compacta (SNc). This results in a loss of movement due to reduced excitation of the direct pathway and reduced inhibition of the indirect pathway.
Parkinson’s Disease has a number of classical symptoms:
- Resting tremor (shaking that is more likely when the limb is relaxed), typically described as ‘pill rolling’ - the mechanism of the tremor is unclear, but may be related to the dysfunction of the indirect pathway which would normally suppress unwanted movements.
- Rigidity, typically described as ‘lead pipe’ - another unclear mechanism, but may be related to lack of coordination between muscle groups.
- Bradykinesia or slowed movements - slowed movements are caused by loss of the excitatory pathway.
- Hypophonia or quiet speech results from bradykinesia of the larynx
- Micrographia or small handwriting results from bradykinesia of the hands
- ‘Mask-like facies’ is the typical description of the appearance of someone suffering from bradykinesia of facial muscles.
Diagram - The motor pathways in the brain, and the pathologies of Parkinson’s Disease involving the substantia nigra pars compacta
SimpleMed original by Dr. Elena Perez
Another extrapyramidal disorder of movement is Huntington’s disease (also known as Huntington’s chorea). It is a genetic disease inherited via an autosomal dominant pattern (the faulty gene is on a non-sex chromosome, and one copy is enough to cause the disease) that causes progressive symptoms, usually starting between 30 and 50 years of age, though it can start much earlier or later.
It is associated with progressive decrease of inhibitory neurotransmission from the striatum via the indirect pathway, leading to increased activation of the thalamus and the motor cortex. This leads to increased involuntary movement referred to as chorea (dance-like movements). Other features include dystonia (sustained muscle spasms that twist the body into abnormal postures), loss of co-ordination and cognitive decline.
Diagram - The motor pathways in the brain, and the pathologies of Huntington’s Disease involving the progressive loss of the inhibitory neurones in the indirect pathway
SimpleMed original by Dr. Elena Perez
Hemiballismus is a very rare extrapyramidal movement disorder. It is the result of damage to the subthalamic nucleus (STN) which can happen from a lacunar stroke (a small stroke deep in the brain) for instance, and it results in unilateral explosive or ‘ballistic’ movements, on the side of the body opposite to the damaged nucleus.
Diagram - The motor pathways in the brain, and the pathologies of Hemiballismus involving the subthalamic nucleus
SimpleMed original by Dr. Elena Perez
The cerebellum is usually kept separate from the extrapyramidal motor system (in clinical use, extrapyramidal disorders are disorders of the basal ganglia), but it interacts closely with the basal ganglia and motor cortex to modulate movement. The cerebellum sits behind the fourth ventricle, meaning cerebellar lesions (e.g. tumours) can result in hydrocephalus (build-up of cerebrospinal fluid in the brain). It is divided into two lateral hemispheres, separated by the vermis (midline). The vermis is responsible for the trunk, whereas the hemispheres coordinate the corresponding ipsilateral side of the body. The cerebellum has three peduncles (thick bundles of nerve fibres that connect it to the brainstem, different to the cerebral peduncles). The superior peduncle connects to the midbrain, the middle peduncle to the pons (the middle part of the brainstem), and the inferior peduncle to the medulla.
In very simplistic terms, the cerebellum works with the basal ganglia by deciding on the sequence in which the movements identified by the basal ganglia should be carried out. It does this by using sensory information on proprioception (the sense of where the body is in space) from the ipsilateral spinal cord, and information from the contralateral cerebral cortex relayed through the pons. This means that signs of cerebellar damage occur ipsilaterally because of a double decussation (crossing to the other side twice): the pathway from the cerebellum to the motor cortex crosses to the opposite side, and the corticospinal motor pathway crosses back in the medulla.
Signs and symptoms of cerebellar disease can be remembered by using the following mnemonic: DANISH.
This page keeps the rapid bedside pattern. For the Purkinje-cell circuit (Purkinje cells are the large output neurones of the cerebellar cortex), the deep nuclei (clusters of nerve cells inside the cerebellum), the functional divisions and the error-correction mechanism that explain why these signs cluster, continue with The Cerebellum: Circuits, Coordination and Clinical Signs.
- D - Dysdiadochokinesia or the inability to carry out rapid alternating movements.
- It is thought to result from poor sequencing of movements, for example repeatedly turning the palm down and up (pronation and supination).
- A - Ataxia: poor muscle control and poor co-ordination.
- Often presents with an unsteady gait (walking pattern) as a result of difficulty sequencing muscle contraction. Ataxia from loss of proprioception (the sense of where the limbs are) is a separate type, called sensory ataxia.
- N - Nystagmus
- Flickering eye movements due to reduced co-ordination of the extra-ocular muscles of the eye.
- I - Intention Tremor
- A tremor that worsens as a target is approached.
- S - Slurred Speech
- Poor co-ordination of the laryngeal and tongue muscles (cerebellar dysarthria).
- H - Hypotonia
- Reduced muscle tone (floppy muscles). The mechanism is unclear.
There are a variety of causes that can result in cerebellar disease or symptoms and some common ones useful to know include multiple sclerosis, chronic alcohol misuse, vascular events (such as stroke) or space-occupying lesions (such as tumours).
Edited by: Dr. Maddie Swannack
Reviewed by: Dr. Thomas Burnell and Dr. Marcus Judge
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