Stems Cells and Neuroprotectives By Dr. Richard L. Bruno
POLIO TIPS AND TECHNIQUES By Dr. Richard L. Bruno
Stem cells are remarkable, embryonic “baby cells” that will grow up to be any kind of cell that the body makes. With all the excitement about stem cells curing spinal cord injury, many polio survivors are wondering if stem cells could cure post-polio syndrome (PPS), or even reverse the damage caused by polio itself.
The hope with SCI is that stem cells, injected into the spinal cord, would “bridge the gap” in cut spinal cord axons, which are like long telephone wires that connect brain motor neurons to spinal cord motor neurons and allow the brain to “tell” muscles to move again. This notion requires intact motor neurons below the cut in the cord. And here lies the problem with stem cells “curing” polio or PPS. Even in “mild” cases, the poliovirus killed off at least 50% of neurons throughout the spinal cord. Stem cells injected into a polio survivor’s spinal cord would not have to just bridge a gap, but become new, functioning motor neurons.
What’s more, those new neurons would have to send out their own axons to find and activate the specific muscles that were paralyzed when the original axons disappeared 50+ years ago after poliovirus-infected neurons died, by burrowing inches, or in the case of the leg three feet, through the tissues inside the arms and legs.
Finally, the brain’s motor neurons would have to send out new axons as well, since the brain’s neurons and axons also died. These axons would have to burrow through the entire brain, the brain stem and down through spinal cord to get to the newly-implanted motor neurons— indeed a tremendous tunneling task!
So the idea of rebuilding a polio-damaged spinal cord would require a “hat trick” of creating new brain and spinal motor neurons, new axons tunneling from the brain to the spinal cord and from the spinal cord to the muscles. Reconnecting a lesioned spinal cord would “only” require the physiological “goal” of bridging the gap between cut axons.
Yes, a possible use for stem cells would be to inject them into the brain, as is done in Parkinson’s disease (PD) patients, where they could produce the main brain-activating neurochemical, dopamine, which is decreased in polio survivors and causes post-polio fatigue. But, such injections are not widely accepted even in PD patients yet.
So, if stem cells aren’t the answer, is there anything polio survivors can do to help their remaining poliovirus-damaged neurons? Recently, there has been research on “neuroprotective” drugs, medications that protect neurons’ innards from overuse/abuse that causes post-polio symptoms. Several studies have focused on degenerative diseases, such as Parkinson’s and Huntington’s disease, which involve damaged dopamine neurons. Minocycline, a common antibiotic used to kill a variety of bacteria, and creatine, which helps to provide energy to muscle cells, have been given to PD patients, who showed a less rapid a decline in function compared to those taking a placebo. However, a study comparing creatine and placebo in 60 PD patients found that, while their mood improved and their need for medication decreased, their symptoms did not lessen.
Vitamin E has been found in eight studies to have some neuroprotective effect in PD, while vitamin C and beta carotene were not helpful. Some research even links coffee’s ability to limit blood vessels from opening to protecting neurons against PD, with one cup a day cutting the risk of developing PD by as much as fifty percent. Another dietary supplement, coenzyme Q-10, is being tested to see if it protects PD patients’ neurons.
Huntington’s disease patients have also benefited from potential neuroprotectives. Huntington’s patients given minocycline had slower progression or no decrease in physical ability, thinking and memory. Creatine had similar beneficial results in HD.
Should polio survivors take minocycline, creatine and Vitamin E, or order a Starbucks’ grande, three-shot cappuccino to prevent post-polio brain fatigue? Not yet. There aren’t enough studies to prove that any of these is truly neuroprotective in Parkinson’s or Huntington’s disease, let alone helpful for polio survivors, in which these substances haven’t been studied at all.
Double-blind, placebo-controlled studies of potential neuroprotectives are warranted in polio survivors. For now, the only neuroprotective that we know works in polio survivors is “The Golden Rule:” If anything causes fatigue, weakness or pain, don’t do it! (Or do less of it.)
Dr. Richard L. Bruno is Director of The Post-Polio Institute at Englewood (NJ) Hospital and Medical Center. E-mail PostPolioInfo@aol.com.
THE POLIO CRUSADE IN AMERICAN EXPERIENCE A GOOD VIDEO
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A 41-year-old man developed an acute illness at the age of 9 months during which, following a viral illness with headache, he developed severe weakness and wasting of the limbs of the left side. After several months he began to recover, such that he was able to walk at the age of 2 years and later was able to run, although he was never very good at sports. He had stable function until the age of 18 when he began to notice greater than usual difficulty lifting heavy objects. By the age of 25 he was noticing progressive difficulty walking due to weakness of both legs, and he noticed that the right calf had become larger. The symptoms became more noticeable over the course of the next 10 years and ultimately both upper as well as both lower limbs had become noticeably weaker.
On examination there was wasting of the muscles of upper and lower limbs on the left, and massively hypertrophied gastrocnemius, soleus and tensor fascia late on the right. The calf circumference on the right exceeded that on the left by 10 cm (figure1). The right shoulder girdle, triceps, thenar eminence and small muscles of the hand were wasted and there was winging of both scapulae. The right quadriceps was also wasted. The wasted muscles were also weak but the hypertrophied right ankle plantar flexors had normal power. The tendon reflexes were absent in the lower limbs and present in the upper limbs, although the right triceps was reduced. The remainder of the examination was normal.
The patient's legs, showing massive enlargement of the right calf and wasting on the left
What is that nature of the acute illness in infancy?
What is the nature of the subsequent deterioration?
What investigations should be performed?
What is the differential diagnosis of the cause of the progressive calf hypertrophy?
An acute paralytic illness which follows symptoms of a viral infection with or without signs of meningitis is typical of poliomyelitis. Usually caused by one of the three polio viruses, it may also occur following vaccination and following infections with other enteroviruses.1 Other disorders which would cause a similar syndrome but with upper motor neurone signs would include acute vascular lesions, meningoencephalitis and acute disseminated encephalomyelitis.
A progressive functional deterioration many years after paralytic poliomyelitis is well known, although its pathogenesis is not fully understood.2 It is a diagnosis of exclusion; a careful search for alternative causes, for example, orthopaedic deformities such as osteoarthritis or worsening scoliosis, superimposed neurological disorders such as entrapment neuropathies or coincidental muscle disease or neuropathy, and general medical causes such as respiratory complications and endocrinopathies.3
Investigations revealed normal blood count and erythrocyte sedimentation rate and normal biochemistry apart from a raised creatine kinase at 330 IU/l (normal range 60–120 IU/l), which is commonly seen in cases of ongoing denervation. Electromyography showed evidence of denervation in the right APB and FDI with polyphasic motor units and complex repetitive discharges, no spontaneous activity in the left calf and large polyphasic units in the right calf consistent with chronic partial denervation. Motor and sensory conduction velocities were normal. A lumbar myelogram was normal. Magnetic resonance imaging (MRI) scan of the calves is shown in figure2.
Axial T1 weighted MRI scan (TR 588 ms, TE 15 ms) of the calves, showing gross muscle atrophy and replacement by adipose tissue on the left, and hypertrophy of the muscles on the right, with only minor adipose tissue deposition
The differential diagnosis of the progressive calf hypertrophy is given in the box.
Causes of calf muscle hypertrophy
Chronic partial denervation
hereditary motor and sensory neuropathy
spinal muscular atrophy
following paralytic poliomyelitis
Neuromyotonia and myokymia
continuous muscle fibre activity due to: chronic inflammatory demyelinating polyradiculopathy, Guillain Barre syndrome, myasthenia gravis, thymoma, thyrotoxicosis, thyroiditis