Neurodegenerative Diseases

These are a spectrum of diseases in which the neurons degenerate with time. Neurons are the building blocks of the nervous system in the brain and spinal cord, they do not have the ability to reproduce so once dead they result in permanent changes. Programmed cell death or apoptosis is a natural human process in which cells undergo death after a certain period of time, in neurodegenerative diseases however this phenomenon is far more pronounced in the brain compared to a normal person whose brain undergoes senility. Most of the diseases in this spectrum don't have a definite cure but they can be managed and in some cases slowed down to improve the quality of life. They include:

Alzheimer Disease and other dementias

In dementias brain cells and neurons undergo atrophy which causes a gradual decrease in the ability to think and remember past events; these changes are pronounced enough to cause disruption in day to day life. Problems with language, emotional changes, decrease in motivation, disorientation, mood swings and behavioral issues also exist. Alzheimer is the leading dementia with 60 - 70% cases, it is a genetic disease with the majority having autosomal dominant inheritance, some of the genes responsible are CASS4, FERMT2, INPP5D, SORL1, CD2AP and HLA-DRB5. These degenerative changes are seen in the cerebral cortex, frontal cortex, cingulate gyrus the temporal and parietal lobes and even in parts of the brain stem. Alzheimer starts manifesting in the 40s and 50s and almost always before the age of 65. It begins with short term memory loss which proceeds to forgetfulness of the forgetting episodes and confusion. Eventually it leads to problems with sleep and speaking, repetition of conversations, abusive or paranoid behavior; in a gist the person is unable to form new memories and eventually loses the most recent ones and the person lives in past memories. Despite great attempts to find a way to halt the disease, not much has been achieved to delay its onset and progression. Some of the medicines used include ACH inhibitors (rivastigmine, donepezil and galantamine), the NMDA receptor antagonist memantine and Huperzine A. Atypical antipsychotics are used to control aggression and psychosis.

Parkinson disease

It is the second most common neurodegenerative disease. Parkinson unlike Alzheimer disease affects the motor system, parts of the brain responsible for motor control like basal ganglia, substantia nigra and the midbrain. It is characterized by buildup of lewy bodies in the neurons of the brain due to which neurons lose the ability to secrete enough dopamine. Other areas affected include olfactory bulb, medulla oblongata and pontine tegmentum. Some of the genes involved include SNCA, GBA, PINK1, CHCHD2, DNAJC13 and VPS35. The symptoms are usually called Parkinson syndrome and include shaking, rigidity (cogwheel and lead-pipe), slowness in movement, difficulty walking, postural instability and non-motor symptoms such as disorders of mood, thinking, behavior and cognitive abilities. Like Alzheimer Parkinson disease also does not have a definitive cure but the response to medication is a lot better in Parkinson disease than in other neurodegenerative disorders. Some of the medications include levodopa, COMT inhibitors, dopamine agonists and MAO-B inhibitors.

Huntington disease

Another motor disease, huntington disease also has a genetic predisposition. It is characterized by a general lack of coordination and an unsteady gait, this advances to uncoordinated jerky movements in the limbs (chorea); these are accompanied with a dementia like state. It as an autosomal disease and the Huntingtin gene responsible for making the huntingtin protein is the main culprit. In general the parts of the brain affected include neostriatum, caudate nucleus, putamen, substantia nigra, cerebral cortex, hippocampus, purkinje cells and parts of the thalamus. Again there is no definitive cure for the disease but experimental drugs are being researched, some of those include tetrabenazine, amantadine, remacemide and some neuroleptics and benzodiazepines. Selective serotonin reuptake inhibitors and mirtazapine help with the psychological symptoms.

Amyotrophic lateral sclerosis (ALS)

Also called Lou Gehrig's disease and motor neuron disease is characterized by death of neurons responsible for controlling voluntary muscles. In most cases the cause is not known but around 15% cases are due to genetic susceptibility. In ALS both the upper and lower motor neurons are affected which result in muscle twitching, stiff muscles, and progressive weakness due to decrease in muscle mass. This in turn results in difficulty speaking, swallowing, loss of sphincter muscles and eventually loss of control of muscles responsible for breathing (respiratory paralysis) which is the usual cause of death in most patients. Among the most famous suffering from ALS is Stephen Hawking who has donated a lot to research on ALS. Like all neurodegenerative diseases ALS does not have a cure but can be symptomatically managed with medication like riluzole, baclofen, diazepam, trihexyphenidyl and amitriptilyine; physical therapy and at the end stage with ventilator support.

Other diseases include Prion disease (due to a misfolded protein alpha-synuclein is characterized by tremors, slow movement, balance difficulties, postural instability, muscle rigidity and loss of autonomic nervous system which result in impotence, loss of sweating, dry mouth urinary retention and vocal cord palsy; there is only symptomatic relief with medication), Spino-cerebellar ataxia (are a group of inherited degenerative diseases which manifest as progressively worsening gait, coordination of movements, chorea, cognitive impairment and pyramidalism; they can be autosomal dominant, autosomal recessive or X-linked), Spinal muscular atrophy (autosomal recessive with loss of motor neurons, progressive muscular wasting leading to early death) and Batten disease (an autosomal recessive disease starting as early as 5-10 years of age manifesting as vision problems, loss of speech and motor skills, curvature of the spine and hyperventilation may occur, seizures are quite common; the disease is fatal).

Neurodegenerative diseases are somewhat brutal and probably natures way of telling us how far behind we actually are in understanding how the various organs and human systems work. There is ongoing research to make life better for those suffering with these conditions and hopefully in the near future a break through will come to make the lives of the sufferers easy.