9.15 Neurology of Movement & Diseases of Movement

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15. Neurology of Movement  (Update, 09 Septr 2021)

Descending column of contents in the order that each subject appears in the chapter. 

Neuroanatomy of Motion - Motor Control Cerebral Cortex 
The Governors of Body Movements
Hard-wired Genetic Program for Movement by Muscles
Molecular Motors :
 The throttle of Motor Movement,The Basal Ganglia;.

Diseases of the Basal Ganglia - Parkinsonism, Huntington's Chorea and the Tremors
The Cerebellum and Its Diseases   

Disease of  Motor Neurons
The muscle weakening of aging
the muscle paralysis in brain stroke
Medications and other system dysfunctions that may affect Muscles
Causes & prevention of brain diseases affecting muscles

Neuroanatomy of Motion - Motor Control Cerebral Cortex 

Voluntary muscle (aka striped muscle because of its appearance) is made up of bundles of muscle fibers with attachments to bones. It makes movement by one's will or in response in reflexes in contrast to muscles of the heart and G.I. tract which move constantly, automatically. By effecting movements, the voluntary motor system keeps a stable upright stance and balance by trunk-muscle tension.

Important diseases affecting the neuromotor system are Parkinsonism (The TV personality Michael J. Fox is famous for it), Huntington's (the folk singer Woody Guthrie died of it) Disease, and Amyotrophic Lateral Sclerosis (ALS, or Lou Gehrig's Disease).  

In the below Figure, on the surface of the brain (in top part viewed from its left side), you can see the voluntary muscle control area in the Cerebral Cortex left-side rear part Frontal Lobe (affecting muscles on the right side of body) on the forward lip of the great transverse (Rolandic) fissure (In the Figure, the fissure's anterior lip is to your - the reader's - left). More forward, next, to it is the premotor frontal cortex. 
   Note the Transverse Fissure of Rolando as the somewhat zigzag black line running vertical and slightly obliquely forward down the middle of the brain at the center of the blue area.

In the above figure, you can see one side of the Motor Cortex (one half or side of an ear-to-ear, or coronal section vertically); at a cut that is right-angle downward through the surface point of Fissure of Rolando. Note the cartoon-ish body parts (the Homunculus) stretched over the cortex surface with feet in the middle fissure and upper extremities & head hanging down one side to indicate body movement control areas in the cerebral cortex. Each side cerebral cortex controls the motor power on its opposite side of the body.
The Homunculus is topographic - it indicates that each spot of the cerebral cortex under it corresponds to a localized spot on the opposite side of the body in muscle motor control. 

The corticospinal right and left nerve fiber tracts (shown in the below Figure) are the most direct, central pathways (brain to muscle via spinal cord) for voluntary motor control, starting in the cerebral cortex motor control area (See above Figure). The cortex motor control neuron fibers come together in bundles that make up parts of each cerebral hemisphere's underlying white matter and then run as nerve fiber tracts through the brain stem with a left to right, right to left great crossing in the lower medulla (the so called Pyramids decussation). About 85% of the fibers make the crossing. So one-side of the motor cortex mostly controls its opposite-side motor action and this is expressed in brain strokes where right side brain damage makes left side body weakness and vice-versa. (Called "hemiparesis when mild weakness and hemiplegia when major or complete)

Lower Motor Nerve Fiber Innervating Motor Unit of a Muscle: A Macro; B. Micro

Gyr 

Final spinal motor nerve muscle synapse: Final source of innervation of voluntary skeletal muscle is from final-motor spinal-cord neuron, and this figure illustrates the end of its fiber where it releases the amine neurotransmitter acetylcholine (ACh - nicotinic channels) into the motor unit synapse. One lower motor spinal or cranial nerve neuron and its nerve fiber innervates each muscle unit and each unit has up to 1000 muscle fibers part of a larger muscle. In humans the ACh at the synapse receptor site causes the muscle fibers contractions and then the ACh is removed by the enzyme acetylcholinesterase that cuts it into the acetyl and choline molecules, and the choline molecule is put back in the nerve-fiber synapse terminal area to make more ACh. 

(Main Text) At each spinal cord level, upper motor neuron fibers from motor cortex in upper brain leave the white matter of the spinal cord, enter the cord's gray matter, and plug into (synapse with) a final-spinal motor-neuron that carries the signal to the target muscle fiber units. The synapse of the upper-motor-neuron fiber into the final-spinal motor-neuron transmits the signal in the spinal neuron's axon-fiber via ventral spinal roots at each descending spinal level. The spinal motor neuron's post-synapse fiber then plugs into the local level muscle unit it is destined for (See above figure). The locations (topography) of body muscles movements seen in the motor cortex (First Figure on top) continues in the axon motor tracts in lower brain and in the spinal cord motor nerve bundles (tracts). This becomes important in localizing the effect of vascular-disease strokes in the brain or in damage to spinal cord. The higher the damage in spinal cord, the more massive the paralysis. 

  A summing up point on final spinal motor neuron: Keep in mind that the information passed into the muscle fiber units by the final spinal motor neuron is not just an order to contract this fiber; It is the sum of all of the other parts of the brain that also have input to motor actions. So it may contain direction, force and purpose of muscle contraction.   

It should be kept in mind that the signal to a muscle fiber unit from a final-spinal neuron axon, although mainly transmitting from the motor cortex, carries combined information of many parts of the brain (motor cortex, basal ganglia, cerebellum sensory cortex), i.e., it is a converging signal point - from the many plug-ins.

When the spinal cord is cut or badly damaged at level of the spinal segment, Cervical 5 or higher, all 4 extremities become paralyzed (quadriplegia – cf. the late Superman actor Christopher Reeve). If the cut is above Cervical 3, the lung's diaphragm muscle is also paralyzed and the condition may be referred to as pentaplegia. It is, obviously, the most serious and requires endotracheal intubation and mechanical ventilator. If a spinal cord cut is below Thoracic-1, the upper body and its extremities are spared from the paralysis but, still, at Th-1 the rib muscles of breathing are affected, the higher up, the worse the affect on breathing. 

The Governors of Body Movements
The above description of control of movement is essentially a simplified description of actual human motor control as when we walk, stand still, reach for something, etc. It is a very centralized view, a scaffolding so to speak. It suggests a pure top-down effect, i.e., the cerebral cortex decides to walk so it sends signals down to the spinal cord that affect all the muscles involved in walking. But this alone would lead to a kind of very gross, Frankenstein-monster stumbling, lurching effect. It needs smoothing out by a kind of throttle-up or -down of the motor power and it needs fine coordination of opposing muscles in each movement; plus, in addition to those, it needs feedback from sensory nerves.
   Also to consider is the development of movement control. In the descriptions of movement we are really thinking about a fully developed adult. Obviously a newborn infant has no control over its limbs or stance. How is that attained?
   So in explaining adult motor movement we must next insert at least 2 big factors into the simplified motor cortex picture of movement control that starts this chapter: the developmental and also the modulation (throttle up or down) aspects of movement; in the latter case meaning the underlying attached governors of gross cerebral control that smooth out and coordinate movements.

Hard-wired Genetic Program for Movement by Muscles
We are born with inherent movement programs called CPG ( Central Pattern Generator Programs) that have been built into our DNA by millions of years of evolution. These CPGs start the key survival movements of walking, running, jumping, reaching. The CPG in humans is not fully developed at birth; the full development occurs during the first years of life and this explains why humans start to walk within a certain age range and never before and if they cannot walk they cannot learn beyond a certain age range. Each species is different, serving the needs of  surviving in its environment. For example, animals like the horse that need to run from earliest age to escape hunters, can run almost as fast as their mother within hours after birth. In humans as they develop, these are not smooth movements as when we normally walk but rather jerky. But they serve as the core of our natural movements. Take walking as an example? A person starts with a motive to walk that originates in the pre-frontal lobe neurons of his brain, based on the cognitive process that says Now I shall start walking in this or that direction. The signals to start walking then go to the motor cortex neurons of all the muscles involved in the act of walking. From these motor cortex neurons  and the spinal cord neurons the basic CPG for starting walking is signaled to the motor neurons involved in walking. But in a human it takes years of training before the habitual CPG of walking is perfected. So that is the developmental phase of muscle movement which is the first key at the start. Now to the governors of smooth, coordinated movement.

Molecular Motors : The electron microscope has shown that on the nano (one billionth of a meter) level there are nano ultramicromotors of many shapes that are the final effectors of all our movements. It's like an Alice in Wonderland level of smallness. 


The throttle of Motor Movement,The Basal Ganglia;.
In discussing the cerebral motor cortex, keep in mind, we are describing a section of a several millimeter, 6-layer surface covering of the brain you view externally, on the left and right cerebral hemispheres. Below those surface cortex layers are large areas of the white matter, which is mostly myelin-sheathed nerve fibers running to and from the cerebral cortical neurons to connect with neurons lower down in the CNS. This area of white matter beneath the cerebral cortex may be referred to as the subcortical, part of the outermost brain (telencephalon). Its under parts are from the diencephalon and below that, the midbrain, or mesencephalon..  Within this white matter are islands of gray matter, subcortical nuclei - the left & right thalamus and just beneath it the single hypothalamus, and on each side, the basal ganglia, and amygdala. Especially the thalamus and BG are important moderators of motor action.

The Thalamus and Basal Ganglia
The major subcortical structures for body movement are the right and left thalamus and the right and left basal ganglia (the BG). 

Note the basal ganglia are paired left and right. 

 The Thalamus and BG are groupings of neurons that have a specific function in the governance of body movement. (It is not their only function.)The connections between the cerebral motor cortex, the BG and the thalamus form a triangular circuit. It starts with the cerebral cortex neurons signaling the BG neurons a need to throttle up or throttle down the gross muscular movement and the BG neurons responding to the "request" signal by either lessening or increasing their inhibition or no-inhibition signal which is passed through the thalamus neurons and from the thalamus back to the motor cortex. The BG is continuously issuing a more or less inhibitory signal to the motor cortex via the thalamus (You might call it a mid-throttle-down setting; in neurophysiologic term, tonic inhibition). When it needs a more powerful movement, more specifically directed to a particular purpose (A baseball pitcher using his left arm to pitch the ball), the cortex signals the BG to lower its inhibition for the left arm motion and this is immediately done and passed back through the thalamus to the cortex and the left arm makes a more powerful throw than previously. And vice versa when less power is needed. This gives an idea of the governing function of the BG in ramping up or damping down a particular movement but it is rather a simplification of the fact that the BG consists of several smaller bodies that together act to not only ramp up or damp down the power of a muscle movement but also to direct its action for a particular purpose

   A dramatic effect that comes from the BG’s subthalamic nucleus Is its ability to suddenly stop an action—-to just say No! (Ala Nancy Reagan.) This is based in one’s BG computing that what seemed a good, pleasant action, i.e., gets computed as having terribly bad, long-term consequence. Apparently Abe Lincoln got it when he opted out of his first decision to marry Mary Todd.  Considering the final outcome, he should have followed his 1st intuition, I believe.

Diseases of the Basal Ganglia - Parkinsonism, Huntington's Chorea and the Tremors   
Two diseases of the BG are Parkinson Disease and Huntington's Chorea. In Parkinsonism, the cells of the BG that produce the neurotransmitter Dopamine are gradually destroyed by disease. The result is a neuromuscular disease of abnormally high motor inhibition where the patient has trouble initiating any movement, and where the movements in general are sparse and slow. (Many late Parkinsonism patients find that their feet seem to be glued to the floor when they stand and try to walk, but once movement has begun, their gait may become almost normal; at an earlier stage it’s called “freezing”, where one finds oneself standing in place unsure how to direct one’s feet.) That is one observation of Parkinson Disease - made famous recently by Michael J. Fox, the TV personality. A Parkinson patient does not move much, and when he does move he takes more time than normal to start and he moves very slowly and sparsely. And because the moment-to-moment muscle governance of the 2 sets of muscles (agonists and antagonists) that both effect the particular movement and prevent it from overshooting are interrupted we see a gross tremor particularly of the hands, which typically is at its worst when the patient is not concentrating on an activity. (resting tremor). Of course, this is the picture of full-blown Parkinsonism but the disease takes up to 20 to 30 years and much of the early part is minor symptoms. There is a good relief of the symptoms by the use of L-DOPA but important that its use be supervised by experienced physician.  Also to be mentioned that this is describing typical, so-called idiopathic (cause unknown) Parkinson disease (IBD).  Many other causes of Parkinsonism are seen: mostly drug induced or genetic). IBD progresses from a first symptom in middle age to, often (and also, too often), to dementia and death 20 to 30 years later. It’s symptoms at first respond very nicely to Levo-dopa medication but eventually it becomes refractory to L dopa.
Here is description in 2020, of IPD from one who got it: “My PD life: I had twitching fingers, difficulty swallowing, and a few falls in 2015 (age 60). My GP told me it was aging. Saw a neurologist in Oct. 2016 who diagnosed it as Parkinson’s. Since then I’ve had leg tremors, general slowness and fatigue.  Cognitively, I have trouble dual tasking and have difficulty holding a thought. I may start Sinemet (Ed.: Carbi/Levo-dopa, aka, Sinemet) next month; (He did!) Made it almost 5 years without it. My neurologist was impressed. Part of my success is exercise 4 to 5 days a week. I have shouted in my sleep but I don’t thrash about (cf. REM movement sleep disorder predicting Parkinsonism). I drool a little and sometimes go into aspiration-triggered coughing fits. Very minor bouts of constipation.”

   In Huntington's chorea (aka "Huntington disease") an opposite effect is seen: Because of too little inhibition, there are an excess of movements and they are sometimes sudden, forceful and uncontrollable (jerking, flinging). Huntington's is a more malignant disease than Parkinsonism with bad psychiatric complications and loss of cognitive power and death 15 to 20 years after onset often from swallowing difficulties complicated by aspiration pneumonia  It is inherited as an autosomal dominant gene. Either parent can pass the gene to all the children and it only needs one copy of the gene to be expressed. Furthermore it involves a most unusual genetic mechanism —- CAG gene expansion whereby multiple copies of a small section the gene on chromosome 4 abnormally repeat its Cytosine-Adenine-Guanine triplet in unpredictable number of repeats that produce the amino acid glutamine many times and make its protein toxic to brain tissue. More than 35 repeat CAG triplets starts the risk to develop HD and 41 or greater repeats guarantees that a child with huntingtin gene will develop HD. The important point is that tissue can be tested before the disease develops and even in a pregnant woman’s embryo or fetus (through amniocentesis) to predict often with certainty the risk that HD will develop. The consequences of such prediction are profound and require careful counseling. 

The Tremors: Hold your arms out in front of you with fingers extended and wide apart. You may or may not notice a very slight tremor, so-called essential tremor which is not a sign of disease. But if you note a gross tremor, so gross that a sheet of paper won’t stay quiet you have an abnormal resting tremor, an early sign of Parkinsonism (almost always starting on one side or the other). Next try pointing with a finger and as you point try to touch the object you are pointing at. If your tremor starts or worsens as you point and try to touch, you have an action tremor, a sign of cerebellum disease. These are simple tests and there are more types of tremors but most can use this model to predict either basal ganglia (Resting tremor of Parkinsonism) or cerebellar disease (Action tremor).
    Internal tremor is a tremor that seems to come from inside the body. (The patient usually points to the stomach area) It comes on usually in night-time episodes that prevent sleep and cause high anxiety and goes away during most of the day(time. It is a not uncommon complaint of younger women and starts acutely after psychic trauma and may last for months but gradually disappears. It is a purely psychogenic, so-called conversion disorder. A physician should try to sympathetically explain it and not try to dig too deeply into it. Inevitably such patients get medical checks which are mostly normal.  Always disappears with tincture of time but may take months or years.  (Not related to PD; purely psychogenic.)

The Cerebellum and Its Diseases  
 The Cerebellum is the other brain structure that involves governance of voluntary movements. Its effect on movements might be described as mathematical. It is a structure that measures time and distance and it is not only involved in voluntary muscle movement but influences all modes of thinking that need mathematical analyses. In voluntary motions, the cerebellum is responsible for good coordination, for hitting the mark exactly on the correct time. For example a baseball fielder catching a hit ball, a violinist choosing exactly the right second to play the right note on the correct string. And the cerebellum, in contrast to the BG, is continually, immediately receiving, instantly, many signals from the whole body's sensory and motor systems; it knows, second to second exactly, in relation to your body, where everything is in space and time. Not only from the sensory system which is feedback and often too slow to affect outcome but the cerebellum actually gets quick feed-forward side messages aka efference copies of immediate muscle actions in the microseconds before the action and it can compute and correct potential errors in aim.
   The cerebellum is located piggy back on the brainstem pons beneath and behoind the main brain. It has a direct nerve bundle connection from left and right spinal cord giving it immediate access to all the sensory info coming into the body from the periphery, and a connection to the cerebral cortex motor area for signals to and from. It does not rely as much on the thalamus to pass its governor signal back to the cortex, as the BG does; rather it needs a more direct signal to feed the cortex instantaneously its instructions for mathematical precision. And it is constantly sending an excitatory signal (opposite of the BG's inhibition) to the motor cortex controller which has the effect of the BG throttle internally inhibiting that signal temporarily for the necessary coordination. This type of control ensures almost instantaneous changing modulation of muscle movement necessary in real life situations. (You are about to be hit by a car and need to immediately gauge how fast and what power you need to jump out of the way; this also needs input from the BG's subthalamic nucleus.)
   Diseases of the cerebellum when they are not inherited in DNA are mostly due to alcoholism and other toxins and to cerebrovascular strokes of the posterior brain blood circulation. They cause an in-coordination that is best tested for by trying to touch the tip of the nose with each index finger while your eyes are shut tight. If you have trouble with right or left cerebellum respectively, you will have trouble touching the tip of nose on right or left respectively. Note that the cerebellum, in contrast to the motor cerebral cortex does not have crossed signals, i.e., the right cerebellum affects the right side of the body and the left affects the left side. Cerebellar disease also gives a gross, obvious tremor, but in contrast to the BG tremor of Parkinsonism, which is seen best at rest, the cerebellar tremor is brought out by reaching for something so it is called intention tremor.

 So to sum up: The motor cerebral cortex neurons give a gross control – an on-off digital but not fine-tune analog. If we only had motor cortex control, we'd walk around like the Tin Man in The Wizard of Oz. For fine control and mathematical coordination it needs the governor signals from the Basal Ganglia and the mathematically coordinating Cerebellum. And it also needs the sensory and vestibular (sense of balance) and visual input and reflexes of the spinal cord to give the voluntary motor system the smooth, precise movements we all need in order to navigate successfully through our lives. And do not forget you are born with a basic DNA program for many movements - walking, talking, etc. - that need(s) training and maturation.

Disease of Motor Neurons starts by destroying motor neurons of spinal cord or, by destroying their axon bundle and cuts off their connection with the final-spinal motor-neurons. The more neurons or fibers damaged, the greater the loss of voluntary muscle control. These are called spinal atrophies and Lou Gehrig’s disease is prime example.

The muscle weakening of aging is a result of gradual loss of motor neurons and muscle cells from wear and tear of living long and not paying attention to health factors such as keeping low cholesterol, normal low blood pressure and normal blood sugar and normal low body weight. It gives old age marche a petit pas (the small-step gait of the very old).

Lou Gehrig's Amyotrophic Lateral Sclerosis (ALS) is a degenerative disease mostly of final-spinal and cranial nerve motor nuclei. (Also may affect brain) Most victims of ALS are dead due to respiratory failure after the muscles of respiration lose their motor nerves usually several years after the disease discovery. Its main and striking symptom (also a sign) is a widespread, progressive twitching called "fasciculation" of small muscle units. Normal persons may at times of stress notice fasciculations, especially around the eyes; but in ALS it is widespread and progressive. The Lou Gehrig type ALS is acquired and although the inciting factor is not known I strongly suspect a life in heavy sports, as Lou Gehrig had, is one cause. The DNA genetic variant ALS is the type we saw in the famous physicist Stephen Hawking and, as everyone by now knows, can be weathered through if you have enough money for assistance and physiotherapy. (Died 2018, age 76, after long fight against the illness.) Research into the inherited form shows it is a disease somehow connected to toxicity of super-oxygen radicals and suggests a lifetime high intake of a good antioxidant like vitamin C might prevent or ameliorate its effects. But that is a guess. Nevertheless it is a good reason to take megadose (2 to 6 grams a day ) of the inexpensive, nontoxic vitamin C.

In the muscle paralysis of brain stroke, (9.20 Secrets of Brain Strokes - Prevention & Relie... ) the blood supply to the cerebral cortex motor neurons or their axon bundles is suddenly cut off because of hemorrhage or blood clot in a cerebral or carotid or vertebral artery or branch, with sudden loss of power. Based on the location of the affected neurons in right or left side of the upper CNS, a stroke will affect the opposite side of the body. A less frequent (but very dramatic) cause of stroke is a traveling blood clot (embolus) from the left heart to block an artery in the brain, most frequently caused by the irregular heartbeat atrial fibrillation. In a stroke, when the affected final-spinal motor-neurons are released from motor cortex neuron inhibition control (by brain stroke or high spinal damage), the muscle units they control will go into spasm after a brief complete flaccidity. The spastic paralysis is typical of upper motor neuron/tract damage from brain stroke or high spinal cord damage. It contrasts to disease of lower spinal cord that leads to a permanent flaccid paralysis of movement. A stroke patient needs rehabilitation to prevent a permanently flexed position of hand, arm or leg from spasms of muscle that cause lower part of extremity to flex on the joint and not to relax.  

Medications and other system dysfunctions that may affect Muscles: A well-known affect of a medication is the myopathy of the Statins, which are used to lower the bad cholesterol. This affect is due to overdose and may be detected by an elevated creatine kinase on the routine blood test. It should not be a reason to avoid Statin drugs which are very good for lowering bad cholesterol but it is a warning to monitor the muscle effect by testing.  And of course many psychotropic medications cause abnormal movements.
  A rather common muscle complaint of old age is degenerative collapse of the lumbar spine due to old age osteoporosis with pressure of the nerve roots to the muscles of the thigh and aches of those muscles to the extent that walking may be compromised. It is a best reason to pay attention to your back bones starting age 20 by good calcium intake and avoiding heavy exercise or sports that may injure the back. Especially when walking on ice in winter. 

Causes & prevention of brain diseases affecting muscles: These are due to brain neuron death by trauma (head banging), toxin (excess alcohol, tobacco, street heroine and cocaine & metamphetamines), bad nutrition (high cholesterol, diabetes) or infection with abnormal immune response. Also as mentioned, caused by the affect of super oxygen radicals. The most frequent causes of abnormal muscle movements today are psychotropic drugs used against schizophrenia and other psychoses, and as mentioned, Parkinsonism.  Best prevention is to live a thoughtful life not centered on sports; a healthy life not involving unnecessary medication or street drugs; and a hygienic life that avoids infection like HIV/AIDS. And get immunized with safe vaccines. Also, avoid excess muscle building. Do not lift heavy weights or run a mile. Such exercise causes abnormal hypertrophy shortens life of muscle, hastens muscle weakness and is responsible for too many falls and fractured hips and traumatic brain hemorrhage in old age. Use your muscles for normal chores, get normal exercise by walking, and you will move best into old age. And never forget keeping a low cholesterol, a normal low body weight and a normal low blood pressure and normal blood glucose - all by moderate eating, avoiding salt and fats, or if you can't manage by these alone, using good medications like statins (Lipitor, etc.) to lower cholesterol, ACE inhibitors to lower BP, and beta blockers to keep a normal heart rate. And take vitamin C as mentioned.

    END OF CHAPTER. To read next click 9.16 .Pain Explained Neurologically