Chronic Degenerative Disorders

In my last post, I wrote about chronic, but non-progressive brain disorders. In this post, I will write about degenerative disorders- that is, those that get worse over time.

Multiple Sclerosis

Multiple sclerosis is a disease in which there is demyelination of central neurons (that is, neurons in the brain and spinal cord). There is also inflammation that produces plaques, particularly in the brain stem, ventricles and optic nerve. Onset of multiple sclerosis usually happens at around 20-40 years of age. Unfortunately we don't know what causes it, but it seems to be more common in females, as well as in people living in temperate climates, so maybe vitamin D plays a role.

Symptoms of MS include bladder or bowel dysfunction, progressive muscle weakness, paresthaesias, fatigue, mood issues including depression and euphoria and vision issues including diplopia ("double vision") and scotoma (seeing a fuzzy patch somewhere in the field of vision). These symptoms can wax and wane, in exacerbations and remissions. Hence, an MRI or a spinal tap showing protein or lymphocytes in the CSF may be required for a more definitive diagnosis.

Unfortunately there is no cure for multiple sclerosis, but interferon, monoclonal antibodies and glucocorticoids to reduce inflammation may help, as well as avoiding exertion.

Parkinson's Disease

Parkinson's Disease affects the basal nuclei, especially the substantial nigra. The basal nuclei are usually involved in trunk and proximal movement, starting and stopping movement and slow and sustained movements. Hence, issues with this area cause symptoms such as a resting tremor (you're unable to stop movement, so you're still shaking a bit even when you don't want to), rigidity, bradykinesia (slow to start movements), difficulty swallowing and walking with a shuffling gait and stooped posture. In later stages, orthostatic hypotension (inability of the body to adjust blood pressure when you stand up) and dementia may also be a problem.

Dopamine appears to be deficient in Parkinson's, or at least not in balance with ACh, which may be too high. Hence, treatments for Parkinson's include L-dopa, which is a dopamine precursor able to cross the blood-brain barrier, and anticholinergics. Exercise may also help patients.

Huntington's Disease (a.k.a. "Huntington's Chorea")

Huntington's Disease also affects the basal nuclei, but it affects a slightly different area called the caudate nucleus, and there appears to be some brain atrophy with this disease. It also involves different neurotransmitters: GABA and ACh appear to be deficient here. This results in choreiform (jerky) movements (hence the nickname "Huntington's Chorea") as well as mood swings, poor judgement and memory lapses.

Unlike many other brain disorders, Huntington's Disease is one that we do know the cause for. It's a genetic disease which is autosomal dominant. Patients with the defective gene begin having troubles at around 35-50 years of age.

Amyotrophic Lateral Sclerosis (ALS) (a.k.a. Lou Gehrig's Disease)

ALS is a disease in which there is degeneration of motor neurons, such as those in the lateral corticospinal tracts. There is, however, no inflammation, and sensory and autonomic nerves are not affected. Interestingly enough, 20% of patients with this have a mutation in the gene coding for superoxide dismutase, which, as I said here, is one of the enzymes that helps us get rid of free radicals.

Onset of ALS usually happens at around 40-60 years, and is more common in males. If upper motor neurons are affected, spasticity is likely to result; if lower motor neurons are affected, paresis is more likely to result. ALS affects distal areas first, before moving inwards. Speech and swallowing can also be affected. Eventually, the disease can progress to respiratory failure.

Dementia

Dementia, which is loss of cortical function, is usually caused by Alzheimer's (which I'll cover soon) or vascular injury. Symptoms include language difficulty, innumeracy, loss of motor coordination, personality changes and memory problems. These memory problems can be distinguished from regular forgetfulness in two main ways. Firstly, people with dementia still struggle to remember things even after given clues to aid in recall. Secondly, they often struggle with computational (numeracy) tasks.

Alzheimer's Disease

Alzheimer's Disease, as I just alluded to, is the most common cause of dementia. There are several brain changes that occur in Alzheimer's, most of which can unfortunately only be detected during an autopsy. These include beta-amyloid plaques, which are clusters of degenerating nerve terminals around an amyloid core, and neurofibrillary "tangles," which are clumps of neurons caused by the Tau protein (these can, however, be seen even in those that are not experiencing cognitive decline). Changes that may be detectable during the patient's life include cortical atrophy, dilated ventricles and widened sulci. However, the sensory cortex is usually fine. Unfortunately, the cause of Alzheimer's is unknown, but it may be genetic as there is a high incidence in patients with Down Syndrome. (Chromosome 21 also happens to be the location of the amyloid gene.)

Alzheimer's Disease progresses in stages. In early stages, patients can get lost easily, lose their sense of humour and become withdrawn. As the disease progresses, they can become confused in familiar places, struggle with daily tasks and communication. In late stages, patients may have motor issues (including incontinence) and lose awareness of their surroundings.

There is no cure for Alzheimer's, but maintaining a daily routine with exercise can help, as can treating any anxiety issues that the patient may have. Low ACh has been associated with Alzheimer's, so inhibitors of cholinesterase (an enzyme that breaks down ACh) may be used, but these have so far only shown limited success. In later stages, patients may need help with tasks such as feeding, particularly if they are having trouble swallowing.

Schizophrenia

Now we move into the world of mental disorders- well, kind of. We're only going to cover schizophrenia in this course, because there simply isn't any time to cover more.

Schizophrenia is a mental illness in which patients lose touch with reality. Symptoms can be divided into "positive" (i.e. presence of abnormal symptoms) and "negative" (i.e. absence of normal traits). (Don't confuse "positive" with "good" here- all of the symptoms are shit.) Positive symptoms include delusions, bizarre behaviours, paranoia, incoherence and hallucinations, whereas negative symptoms include feeling "flat" and apathetic, anhedonia (loss of joy) and social withdrawal.

There are some brain changes implicated in schizophrenia, such as reduced grey matter in the temporal lobes and reduced blood flow to frontal lobes, as well as some possible changes with regards to neurotransmitters such as increased dopamine, reduced serotonin and possibly issues with glutamate receptor function. Dopamine can be decreased with dopamine antagonists, though these can have unpleasant side effects such as tardive dyskinesia (repetitive, involuntary movements). Serotonin can be increased with SSRIs (selective serotonin reuptake inhibitors), which inhibit the reuptake of serotonin into neurons, so that there's more bouncing around in the synapse stimulating the next neuron. Interestingly enough, LSD, a serotonin antagonist, and PCP ("angel dust"), a glutamate receptor blocker, can both mimic the symptoms of schizophrenia, such as hallucinations and paranoia.