WHAT are NEURODEGENERATIVE DISORDERS?

The term “neurodegenerative disorders” is an umbrella term for a range of conditions affecting neurons (nerve cells) in the brain and spinal cord. Neurodegeneration refers to progressive death of neurons. Because neurons cannot be replaced like many other cell types in the human body, death of neurons inevitably leads to progressive dysfunction. While many neurodegenerative disorders are known to be inherited (i.e. due to genetic abnormalities), the cause in others remain unknown despite intense efforts to identify the causes. The best known examples of neurodegenerative disorders for which the causes are unknown are motor neuron disease (MND) and Parkinson’s disease (PD). Although some forms of MND and PD are due to genetic abnormalities (familial MND and PD), most cases are not familial. This is referred to as sporadic PD or MND. Most experts believe that sporadic disease is due to a combination of genetic susceptibility and one or more (as yet unidentified) environmental factors. Probably the most important implication of this is that, because the cause is either unknown or genetic, there are no effective treatments that can stop the progression or significantly alter the course of these disorders. Another problem is related to diagnosing these conditions. Where the genetic mutation is known and the test is commercially available, confirmation of the diagnosis is relatively straightforward. However, in the case of for example MND and PD, diagnosis depends mainly on the combination of findings on clinical examination and some ancillary tests, none of which are specific for the disorder. This can make an accurate diagnosis early in the course of the disease challenging.

The clinical features of neurodegenerative disorders depend on the particular regions of the nervous system that are affected by the disease process. There is also a significant difference between conditions with regards to the speed at which they progress. For example, MND is a rapidly progressive condition, while the spinocerebellar ataxias generally progress much slower. A few of the more common neurodegenerative conditions in adults are MND, PD, Alzheimer’s disease (AD), Huntington’s disease (HD) and spinocerebellar ataxia (SCA). Other

MOTOR NEURON DISEASES (MND)

MND develops due to degeneration of the neurons of the motor system, i.e. those neurons supplying muscles. This leads to progressive wasting and weakness of limb muscles, bulbar muscles (muscles responsible for swallowing and speaking), and respiratory muscles. The course of MND is generally rapidly progressive, with most people surviving between 2-5 years, although there is a wide variation.

PARKINSON’S DISEASE (PD) AND PARKINSON-PLUS DISORDERS

PD develops due to degeneration of the dopaminergic neurons in the brainstem. This leads to a deficiency of the neurotransmitter dopamine, which is necessary for normal function of the basal ganglia. The basal ganglia are a group of nuclei that is responsible for the control of movement. A deficiency therefore leads to a combination of rigidity (stiffness), bradykinesia (slow movement) and tremor. As these features worsen, it may lead to severely impaired mobility with frequent falls. The early stages of the disease can be controlled by supplementation with dopamine.

Parkinson-plus disorders present in a very similar way as PD, but with additional features, for example prominent eye movement abnormalities in the case of progressive supranuclear palsy (PSP). Most Parkinson-plus disorders are resistant to treatment with dopamine.

ALZHEIMER’S DISEASE (AD) AND OTHER DEMENTIAS

Dementias are responsible for the greatest burden of neurodegenerative diseases, with Alzheimer’s representing approximately 60-70% of dementia cases. Early symptoms include memory impairment, word-finding difficulties, social withdrawal and trouble interpreting visual images.

HUNTINGTON’S DISEASE (HD)

HD presents with progressive loss of memory, personality change and chorea (abnormal movements of the arms and legs. The disorder is inherited and there is usually a strong family history, with either the mother or father affected.

SPINOCEREBELLAR ATAXIA (SCA)

People with SCA present with progressive ataxia (incoordination and poor balance), speech disturbance, and spasticity. SCA is also an inherited condition, and the diagnosis is usually straight forward because of a strong family history and the availability of genetic confirmation.

The commonest neurodegenerative disorders are MND, PD and AD. All three these disorders are predominantly disorders of middle- and older age groups. Worldwide, and also in sub-Saharan Africa (SSA), populations are increasingly living longer. In SSA, life expectancy at birth has increased by approximately 20 years between 1950 and 2010. In South Africa, the number of individuals aged 55 years and older has increased from 1 229 000 to 6 085 000 during the same period, a nearly 5-fold increase. Consequently, the burden of disease of neurodegenerative disorders are increasing. Because people with neurodegenerative disorders have special needs due the disabling nature of these disorders, management is labour- and resource intensive. Unfortunately, due to the disproportionately high burden of disease of infectious and cardiovascular disease in South Africa, resources available for management of the neurodegenerative disorders are scarce, and sufferers are often left to their own devices.