Degeneration of the Nervous System




This grouping is of disorders might better be titled -"Not CP". The main theme is youthful debility caused by genetic errors in nerve and nerve supportive structures. The common result is progressive failure of the neurologic function.

CP is considered a one time injury, not progressive. This distinction blurs a bit when the static damage of CP causes worsening of bodily appearance by way of wear and tear on the skeleton and muscle mechanisms. Further, if CP has seizures as a component, then the seizures can be a source of additional neuron damage and thus there may well be neurologic progression. In CP, other factors may cause real neurologic worsening. Aspiration can lead to respiratory arrest and further neurologic damage. A fall can cause head injury. Things can happed. => CAN <= but not must.

The point is that in the non-CP disorders discussed in this section, no event is required, no accidents or mishaps. The basic structure of the neurons or the tissues that serve the neurons is flawed - genetically. As with Alzheimer's disease, progression is built in.


There is no graceful way to sort these entities as they are all over the place in specifics. The similarities in end appearance muddle categorization by disease features. Basic chemistries are not clear in many, so that leaves category by means - fragmented. By genes, we may well have several differing anomalies that cause the same end defect. Others are yet to be detected.

We wind up with category by method of detection, a path to travel in seeking a diagnosis. We can distinguish (with MRI for example) the white matter from the gray matter. That gives us an artificial but useful categorization. Diseases of white matter, diseases of gray matter and diseases with both white and gray matter degeneration. We have already seen some of these diseases listed under their own headings. Consider this a medical path to arrive at those specifics.

              White Matter:
              Canavan's Disease
                    Krabbe's Disease
                    Metachromatic Leukodystrophy

              Gray Matter:
                    Gaucher's Disease
                    Menkes' Disease

              White & Gray Matter:
                    Peroxisome disorders
                    Mitochondrial disorders
                    Cell filament disorders



White Matter:
What is white matter? Mostly insulation- cell membranes wrapped in may layers - around neurons. Those fatty (myelin is a fat) cell membranes isolate the neuron from the salt water mileau of the body creating an environment that allows much faster and more reliable conduction as well as protection and support of very slim and long neurons.


Canavan's degeneration and

Krabbe's neuropathy  have their own sections.

Metachromatic Leukodystrophy
In the absence of a specific enzyme, cerebroside sulfatase - a flavor of myelin (with a sulphur group attached - called a sulphatide) builds up. This material bloats the cells and gets gobbled by white cells as neuronal elements degenerate. The material gobbled by white cells stains oddly with dyes used to look at cells under the microscope. That is what the name means "oddly colored (metachromatic) weirdness (dystrophy) of white (leuko) cells"

Depending on how fast the milestones go, the onset at about a year old, may be either predominantly NEW  floppyness or NEW unsteadyness. Quickly it becomes both. It is incorrect to call such a new finding "Hypotonia" as a title rather than as a description, as it wasn't there before. The floppyness lessens and high tone follows with severe spasticity and grossly rigid postures dominating. There are other leukodystrophies.

Gray Matter:
Gray matter is essentially neuron cell bodies and nerve structure with less or no myelin components. The way the brain is organized, the gray matter is more centrally located and the white matter covers as a thick mantle. However, that does not mean that there are different cells in the two places as portions of a nerve cell may be uncoated with myelin and other portions coated. Cells in the gray matter may and do extend well into the white matter.

Menkes' Disease has its own section

Gaucher's Disease : Some cases are seen early although most take a while to manifest and do so as swollen liver and spleen (belly looks almost pregnant). In the very young onset the head is extended way back and functions about the neck and pharynx are amiss. The eyes diverge. Skin may look thin and shiny.

Underlying this disorder is accumulation of certain cells related to marrow clean-up cells which are stuffed and choked with lipid (glucosylsphingosine). Somehow this damages adjacent nerve cells.

As bad as this disease can be, and that is very bad, there are partial cases. There are also new treatments in trials that try to unload the buildup that causes the indirect neurologic damage.

Gangliosidoses also, as with Gaucher's Disease, cause organ swelling. The pathologic difference is in the material that backs up and stuffs the cells. There are several enzyme defects with resultant bottleneck blockages in the metabolism that distend neurons with the substances that can not get degraded and eliminated. There are several well known versions of this category which has a well known version called Tay-Sachs Disease. In Tay-Sachs, a specific "ganglioside" builds up behind an enzyme defect. But even this has variations. As the genetic information gets better, we find that there are many ways to have a single protein go wrong or ti disrupt a single process of several proteins acting in concert.

White & Gray Matter:

Mitochondrial disorders have a section already dedicated. A prominent disorder called

 MELAS by acronym has mitochondria disordered (which you can't see) with encephalopathy (diffuse brain dysfunction - something you can suspect by functional problems), lactic acidosis (which might be detected on a blood test or spinal tap) and stroke. The stroke is the big one which often grabs everybody's attention. This stroke does not require some outlandish brain fever or other causal event.

Cell filament disorders
These have been discussed as a generality but without any specific neurologic examples. One example is

Neuroaxonal Dystrophy of Infancy
One of the subcellular filament types skipped over in the section on cell basics is a cell mollecular filament called "neurofilament" as it is a major structural element in nerve cells. At about a year of age sucking falters and eye movements become faulty. The pupils also do not respond appropriately to light. Spasticity follows. Degeneration of the cerebellum might be found on MRI along with loss of both white and gray tissue volume.

Peroxisome disorder - Logically, there ought to be a section on peroxisomes under cell basics as peroxisomes are very Spartan - even primitive - structures found within cells. It is just that there isn't a whole lot to say. They are very tiny sacks of oxidation enzymes. They are cell membrane bounded bubbles found within the cell - smaller than mitochondria - which can self reproduce (without DNA) by growth and pinching off. The peroxisomes use components made by the cell and delivered to the peroxisome.

That is interesting in itself, as we now know of mail delivery diseases within cells. The enzymes that the peroxisome uses are tagged with a specific sequence of amino acids that tell the cell to deliver the protein to a peroxisome. The amino acid sequence is not functional in what the enzyme does, but is an address as to where the protein is meant to be. It turns out that other cell structures also have addresses which are encoded into their proteins. Sometimes that code is on an extra length of the protein which gets snipped off when the protein is delivered. Some of that code also tells how the protein is to be oriented (this end up) and attached.

In the peroxisome are enzymes which take hydrogen from cell substances and in a stepwise way (through the formation of Hydrogen peroxide) oxidize those substances to a form that is no longer toxic and which can be more readily discarded. The peroxisomes are subcellular incinerators. They do not do what mitochondria do, use that oxidation to make fuel, but just detoxify. About 20 to 30% of alcohol is destroyed by these cell units. Urates also go this route. Peroxisomes also chip SOME of the carbon pairs off of fatty acids to produce acetyl Coenzyme-A and thus assist the pathway of breakdown of fatty acids (a job shared by mitochondria).

As the job of peroxisomes is heavy on the detoxification side, we can correctly guess that defects will be prominently noted in organs of detoxification - liver and kidney.


Zellweger Syndrome
We know of a defect in which the address encoded in peroxisome intended proteins is encoded with an error such that the enzymes do not get delivered. The result is empty peroxisomes and a disease called Zellweger Syndrome. It presents as a leukodystrophy . A characteristic high forehead with bull dog fatty neck folds suggests the diagnosis confirmed by lab studies.