Paralysis is the complete
loss of muscle function for one or more muscle groups. Paralysis
often includes loss of feeling in the affected area.
Paralysis is most often caused by damage to the nervous system or brain,
especially the spinal cord. Partial paralysis can also occur in the REM
stage of sleep. Major causes are stroke, trauma, poliomyelitis, amyotrophic
lateral sclerosis (ALS), botulism, spina bifida, multiple sclerosis, and
Guillain-Barré syndrome. Poisons that interfere with nerve function,
such as curare, can also cause paralysis.
Paralysis may be localized, or generalized, or it may follow a certain
pattern. For example, localized paralysis occurs in Bell's palsy where
one side of the face may be paralyzed due to inflammation of the facial
nerve on that side. Patients with stroke may be weak throughout their
body (global paralysis) or have hemiplegia (weakness on one side of the
body) or other patterns of paralysis depending on the area of damage in
the brain. Other patterns of paralysis arise due to different lesions
and their sequelae. For example, lower spinal cord damage from a severe
back injury may result in paraplegia, while an injury higher up on the
spinal cord, such as a neck injury, can cause quadriplegia. Patients with
paraplegia or quadriplegia often use equipment such as a wheelchair or
standing frame for mobility and to regain some independence.
Most paralyses caused by nervous system damage are constant
in nature; however, there are forms of periodic paralysis, including sleep
paralysis, which are caused by other factors.
"Paralysis occurs only when the patient is at rest,
and usually in bed at night. The rest commonly follows a period of unusually
great physical activity and consumption of a high-carbohydrate meal. Observant
patients, realizing that paralysis did not occur while they were active,
rapidly learn to "work off" an impending attack on the appearance
of premonitory symptoms."
Patients with thyrotoxic periodic paralysis have attacks only when they
are thyrotoxic. Graves' disease appears to be the most common cause of
thyrotoxic periodic paralysis, since this disorder represents the majority
of patients with hyperthyroidism. However, it appears that the specific
cause of the thyrotoxic state is not a critical factor for the expression
of the paralytic attacks because cases have been documented in association
with jodbasedow, TSH-secreting pituitary tumor,abuse of thyroid hormone,
and solitary toxic thyroid adenoma. These associations of paralysis with
the different causes of thyrotoxicosis indicate that the attacks are induced
in susceptible persons by a mechanism that is not autoimmune in origin.
Paralytic attacks can be induced by insulin and carbohydrate administration
in hyperthyroid patients with a history of thyrotoxic periodic paralysis
but not in patients with a history of thyrotoxic periodic paralysis who
have become euthyroid.Restoring the euthyroid state in patients with a
history of thyrotoxic periodic paralysis usually prevents the recurrence
of paralytic attacks. However, paralytic attacks recur if thyrotoxicosis
recurs.[2,25] In comparing thyrotoxic patients with recurrent paralytic
attacks and those without such episodes, it was noted that the occurrence
of paralysis was not related to the duration and severity of the thyrotoxicosis.
Thyrotoxic periodic paralysis is most commonly described among Asian men.
Of the 1,366 consecutive cases of thyrotoxicosis in southern Chinese patients,
1.8% gave a history of attacks of paralysis. Case reports from the Mayo
Clinic indicated that the approximate incidence for thyrotoxic periodic
paralysis in a largely North American population ranged from 0.1% to 0.2%,
or about one tenth the rate reported for Asian populations. A review by
Ober of cases from the continental United States showed the distribution
of thyrotoxic periodic paralysis is 45% white, 24% Asian, 15.5% Hispanic,
7% black, 7% American Indian, and 1% others. Review of the literature
indicates that the occurrence of thyrotoxic periodic paralysis is very
rare among blacks. Our cases represent the ninth and tenth reported cases
in black patients.
Thyrotoxic periodic paralysis primarily afflicts men. In the review of
1,366 cases of hyperthyroidism in southern Chinese patients, 13% of the
men and 0.17% of the women had thyrotoxic periodic paralysis.Of the known
factors that provoke the onset of paralysis, it might be suggested that
physical exertion would be greater in men. However, a large number of
Chinese women are engaged in heavy manual labor, making the degree of
physical exertion a less important precipitating factor. In the cases
among black patients, including our 2 cases, eight patients were men and
only two were women.
Although the mechanism of thyrotoxic periodic paralysis remains uncertain,
the two main ingredients that produce a paralytic attack are thyrotoxicosis
and hypokalemia. It has been shown that Na+,K+-ATPase activity in
patients with thyrotoxic periodic paralysis was significantly higher than
in healthy subjects or in thyrotoxic patients without a history of paralysis
despite similar degree of hyperthyroidism. Compared with thyrotoxic patients
without paralysis, patients with thyrotoxic periodic paralysis respond
to thyrotoxicosis with a smaller decrement in erythrocyte Na+,K+-ATPase
activity, however, the difference is too small to represent a useful genetic
marker for this disease entity.There are high levels of immunoreactive
insulin during spontaneous attacks in thyrotoxic periodic paralysis. An
increase in plasma glucose concentration together with abnormally high
levels of serum immunoreactive insulin was observed preceding a spontaneous
attack of paralysis, and the affinity of erythrocyte insulin receptors
was decreased during the attack.] In thyrotoxic periodic paralysis, patients
have been found to have hyperinsulinemia, and this is accompanied by increased
Na+,K+-ATPase activity. Precipitation of an attack by a carbohydrate diet
was associated with only a modest fall in level of plasma potassium but
with a marked rise in total blood cell potassium.
It has been observed that b-blockade with propranolol prevents paralysis,
and this suggests that the development of paralysis is partly influenced
by the hyperadrenergic state characteristic of thyrotoxicosis. Studies
in skeletal muscle have shown that CA++-ATPase activity and the calcium
uptake by sarcoplasmic reticulum decrease during the attack of paralysis
but revert to normal after the attack. The decrease in the activity
of the calcium pump was proportional to the severity of paralysis and
the degree of hypokalemia.
Studies suggest that chronically elevated plasma aldosterone
levels may contribute to the occurrence of periodic paralysis of thyrotoxicosis
in some patients, especially when further stimulated by a prompt increase
in endogenous corticotropin as the result of severe stress, or even a
normal or diurnal rise. In 17 hyperthyroid patients without paralysis,
neurophysiologic evaluation of untreated hyperthyroid patients showed
abnormalities mainly in the proximal muscles, and these findings suggest
the presence of an initial axonal type of mild polyneuropathy.In a study
of 7 patients with thyrotoxic periodic paralysis by using glucose and
insulin infusion, a paralytic attack developed within 90 minutes in 6
of 7 patients.These results suggest that hyperaldosteronism may not be
a trigger for the induced paralytic attack but may be a phenomenon due
to volume depletion and a change in potassium homeostasis induced by glucose
and insulin infusion.
Electromyographic studies in eight Chinese patients with
thyrotoxic periodic paralysis showed that most had a myopathic pattern
during an attack of paralysis that disappeared during remission.The myopathic
changes were a decrease in duration of muscle action potentials, an increase
in polyphasic potentials, a satisfactory interface pattern with reduced
amplitude, and a reduced amplitude of the evoked muscle action potential
on nerve stimulation. Peripheral nerve function was normal in these cases,
and it was concluded that the weakness in thyrotoxic periodic paralysis
is myopathic and that the peripheral nerve function during paralysis is
Light microscopy of the biopsied quadriceps muscles during
paralysis in 17 patients with thyrotoxic periodic paralysis showed no
abnormalities in 23.5%, sarcolemmal nuclear proliferation in 35.5%, atrophy
of muscle fibers in 29.4%, central nuclei in 23.5%, fatty infiltration
in 17.6%, vacuolation in 11.8%, and sarcoplasmic masses in 11.8%. These
muscles were also examined by electron microscopy in 10 patients; the
main changes observed were vacuolation in 90%, mitochondrial abnormalities
in 100%, glycogen granules accumulation in 100%, disruption of the myofibers
in 50%, and changes in the T system in 40%.The light and electron microscopic
changes in the skeletal muscles during paralysis were not well-correlated
with the severity of the muscle weakness of hypokalemia.
In another study, electron microscopic examination of
muscle biopsy specimens made it possible to assume that in thyrotoxic
periodic paralysis, the action of the thyroid hormone not only causes
impairment of the mineral metabolism, but also brings about changes in
the structure of the membranes of the sarcolemma and T system, which leads
to disturbances of conductance of action potential into the fiber. These
changes affect the function of the end cisterns and lead to distortion
of the processes of conjugation of excitation-contraction with resulting
development of paresis and paralysis of muscles.
In animal studies, thyroid hormone appears to regulate
Na channels in cultured rat skeletal myotubes by two opposing mechanisms,
(1) direct stimulation of Na channel synthesis and (2) indirect decrease
in synthesis mediated by an increase in cytosolic Ca+. The results
indicate that thyroid hormone may play an important role in developmental
expression of Na channels in excitable tissue. In rats, triiodothyronine
induced upregulation of the concentration on Na+ channels and Na+,K+ pumps,
which was associated with a progressive loss of contractile endurance.
These observations are important for an understanding of the fatigue associated
with hyperthyroidism and add further support to the hypothesis that muscle
endurance depends on the leak-to-pump ratio for Na+. In rat soleus muscle,
thyroid hormone at physiologic doses seems to be the major endocrine factor
determining the concentration of Na+,K+ pumps in skeletal muscle, and
endurance is a function of the ratio between the concentration of Na+
channels and Na+,K+ pumps. In rat skeletal muscle, the stimulation of
the Na/H antiport by physiologic concentrations of thyroid hormones results
in a dose-dependent increase in intracellular pH.These findings suggest
that thyroid hormones may have an active role in the recovery from muscular
acidosis through direct stimulation of the Na/H antiport.
Studies of the interaction of the thyroid state and skeletal
myosin heavy chain expression in rats suggest that for patients with nerve
damage and/or paralysis, both muscle mass and biochemical properties can
also be affected by the thyroid state. In rat heart, the status of sarcolemmal
Ca+ transport processes is regulated by thyroid hormones, and the modification
of Ca+ fluxes across the sarcolemmal membrane may play a crucial role
in the development of thyroid state-dependent contractile changes in the
heart.In hyperthyroid cats with hypokalemia and skeletal muscle weakness
manifested as ventroflexion of the neck, correction of the hypokalemia
led to recovery in muscle strength.
In the rat brain, Na+,K+-ATPase activity has been noted
to be significantly greater in males than in females, and testosterone
induces an increase in the Na+,K+-ATPase activity. Other studies in rats
showed that hepatic Na+,K+- ATPase activity is inhibited by estrogen.
Progesterone or progesterone derivatives also inhibited Na+,K+-ATPase
activity in the canine kidney and in the guinea pig heart and brain.These
effects of sex hormones on the Na+,K+ pump may contribute to the predisposition
for thyrotoxic periodic paralysis in men.
Unlike familial hypokalemic periodic paralysis, thyrotoxic periodic paralysis
is not usually associated with family history. There is, however, an association
with the presence of HLA-DRw8, and data suggest that this gene may play
a significant role in the susceptibility to thyrotoxic periodic paralysis
among Japanese men. In a pair of monozygous adolescent male twins with
hyperthyroidism, one had thyroiditis while the other had muscle weakness
and paralysis. The finding of HLA antigens A2BW22 and AW19B17 in Chinese
patients with thyrotoxic periodic paralysis but not in patients without
the disorder raises the possibility that these haplotypes may serve as
genetic markers. In a black patient, phenotyping revealed neither of the
two genetic markers previously observed among Chinese patients with thyrotoxic
periodic paralysis, indicating that the haplotypes do not serve as markers
for the disorder in black patients. Although the HLA system has been suggested
to provide a link to a presumed immunogenetic etiology of the thyrotoxic
periodic paralysis, this seems to be an unlikely explanation in view of
the numerous patients with the disorder whose thyrotoxicosis is not related
to autoimmune mechanism. The high incidence of the disorder in Asians
suggests that the basic defect may be genetically determined, but the
defect manifests itself only when challenged by thyrotoxicosis.
The definitive therapy for thyrotoxic periodic paralysis is the management
of the thyrotoxic state by medical therapy, surgery, or radioactive iodine
therapy. The resolution of periodic paralysis with restoration of euthyroidism
has been acknowledged as a universal finding.The Na+,K+-ATPase activity
in RBCs was found to be impaired in Graves' disease, and thioamide treatment
restored the normal activity. One case was an exception, however, because
the periodic paralysis persisted even when the patient's clinical and
laboratory features suggested a euthyroid state. This patient continued
to have symptoms of periodic paralysis when he progressed to hypothyroidism
after radioactive iodine ablation.
Once the paralytic attack has started, administration of potassium is
standard therapy, and recovery of the periodic paralysis may be hastened.
Although the serum potassium level will eventually normalize spontaneously
as potassium moves from the intracellular space to the extracellular space,
the administration of potassium is not done to correct the hypokalemia.
It is given mainly to prevent cardiac arrhythmias that potentially can
be life-threatening. Potassium is usually administered intravenously,
even though there is no proven benefit or advantage in using this method
As potassium is released from the cells into the circulation
during the recovery phase of the paralytic attack, aggressive potassium
administration can lead to hyperkalemia, as happened in our case 2 patient
with a potassium level of 6.1 mmol/L after receiving a dose of only 60
mEq KCl. A patient who had a potassium level of 1.9 mEq/L progressed to
a level of 6.4 mEq/L after receiving 100 mEq KCl intravenously over 10
hours.20 In cases with associated hypophosphatemia, as in our patients'
cases and those of Norris et al and Guthrie et al, it has been observed
that serum phosphate levels returned to normal after giving only potassium.
After initiating the definitive therapy for the thyrotoxicosis,
patients should be advised to avoid precipitating factors while awaiting
normalization of the thyrotoxic state. Others have advocated supplementation
with oral potassium to prevent attacks of paralysis in some patients,
though this approach is not consistently effective. Acetazolamide has
been used in the familial hypokalemic periodic paralysis; however, in
one case a Hispanic man was given acetazolamide for his thyrotoxic periodic
paralysis, which had been mistakenly diagnosed as familial hypokalemic
periodic paralysis, and this resulted in near-total body paralysis 2 weeks
later. In some cases, the efficacy of using spironolactone or aldosterone
antagonist SC942065 in preventing paralytic attacks is well-documented.
b-Adrenergic blockade induced with propranolol therapy has resulted in
marked relief of the episodes of paralysis and is probably the most useful
preventive therapy until a euthyroid state is achieved.
Paralysis in the animal world
Many species of animals use paralyzing toxins in order to capture prey,
evade predation, or both. One famous example is the tetrodotoxin of fish
species such as Takifugu rubripes, the famously lethal pufferfish of Japanese
fugu. This toxin works by binding to sodium channels in nerve cells, preventing
the cells' proper function. A non-lethal dose of this toxin results in
temporary paralysis. This toxin is also present in many other species
ranging from toads to nemerteans. Another interesting use of paralysis
in the natural world is the behavior of some species of wasp. In order
to complete the reproductive cycle, the female wasp first paralyzes a
prey item such as a grasshopper and then places it into her nest. Eggs
are then laid on the paralyzed insect, which is devoured by the larvae
after they hatch. Many snakes also exhibit powerful neurotoxins that can
cause non-permanent paralysis or death.
Paralysis can be seen in breeds of dogs that are chondrodysplastic.
These dogs have short legs, and may also have short muzzles. Their intervertebral
disc material can calcify and become more brittle. In such cases, the
disc may rupture, with disc material ending up in the spinal canal, or
rupturing more laterally to press on spinal nerves. A minor rupture may
only result in paresis, but a major rupture can cause enough damage to
result in complete paralysis. If no signs of pain can be elicited, surgery
should be performed within 24 hours of the incident, to remove the disc
material and relieve pressure on the spinal cord. After 24 hours, the
chance of recovery declines rapidly, since with continued pressure, the
spinal cord tissue deteriorates and dies.
Another type of paralysis is caused by a fibrocartilaginous
embolism. This is a microscopic piece of disc material that breaks off
and becomes lodged in a spinal artery. Nerves served by the artery will
die when deprived of blood. The German Shepherd is especially prone to
developing degenerative myelopathy. This is a deterioration of nerves
in the spinal cord, starting in the posterior part of the cord. Dogs so
affected will become gradually weaker in the hind legs as nerves die off.
Eventually their hind legs become useless. They often also exhibit fecal
and urinary incontinence. As the disease progresses, the paresis and paralysis
gradually move forward. This disease also affects other large breeds of
dogs. It is suspected to be an autoimmune problem.
Cats with heart murmurs may develop blood clots which
travel through arteries. If the clot is large enough to block one or both
femoral arteries, there may be hind leg paralysis because the major source
of blood flow to the hind leg is blocked.
was last modified 09.10, 10 Febuary 2008.