Celiac Disease Prevalence Remains Unknown

According to an article published in the American Journal of Gastroenterology, although celiac disease is common, the prevalence of this disease is actually unknown .Celiac disease is a chronic intestinal disease characterized by atrophy   the villi and malabsorption. Removing gluten from the diet is both therapeutic and diagnostic test because symptoms disappear as soon as gluten is eliminated. In fact, it is not gluten that causes celiac disease, but a toxic protein from gluten, gliadin.

In celiac disease there is an abnormal immune response against wheat gliadin or against other proteins in rye, barley, oats. Although according to the Mayo Clinic-led analysis, 1.8 million  Americans have celiac disease , but the total number of people suffering from this disease is unknown. There are described three clinical forms of celiac disease: symptomatic celiac disease (atrophy of the villi and clinical manifestations), silent celiac disease (atrophy of the villi without clinical manifestations) and latent celiac disease.Regarding the cause of the disease , there were incriminated environmental factors (gliadin, etc), genetic and immunological factors. In children, celiac disease is manifested by vomiting, diarrhea, abdominal distention, muscle weakness, etc.

Celiac Disease

In adults, the most common manifestation is diarrhea. Because of malabsorption, osmotic diarrhea leads to fat feces. Diarrhea is of course accompanied by flatulence and abdominal distension. Sometimes abdominal pain can occur. Also, because of malabsorption, nutritional deficiencies may appear. Due to malabsorption of bile salts , there is a vitamin deficiency, ie A, D, E, K. Therefore, there may be numbness, muscle cramps, tetany, bleeding (epistaxis, bruising), vision problems, infertility,  anemia. Also, peripheral edema and ascites may occur, weight loss, glossitis etc.

Celiac disease can be misdiagnosed , especially when symptoms are vague or when they occur in children. Celiac disease can be confused with certain diseases caused by parasites , like  Giardia or Strongiloides. It also can be mistaken for other diseases that cause malabsorption, such as Crohn’s disease, Whipple’s disease or eosinophilic gastroenteritis. Diagnosing celiac disease is very important because removing gluten from the diet results in complete relief of symptoms. There are situations where patients do not respond to treatment, ie the removal of gluten from the diet. These patients have the so-called refractory celiac disease. In addition, it is good to know that celiac disease causes some complications that may worsen the health of the patient. One complication is ulcerative jejuno-ileitis, characterized by abdominal pain and gastrointestinal bleeding . Another important complication is intestinal lymphoma.

Researchers have tried to find out what is the prevalence of the disease with blood tests and interviews from the Centers for Disease Control and Prevention (CDC).  co-author Joseph Murray, M.D., a Mayo Clinic gastroenterologist, says: “There are a lot of people on a gluten-free diet, and it’s not clear what the medical need for that is.

Dromant HIV

Researchers at the University of North Carolina made a discovery that could provide a new treatment option for HIV infection. Vorinostat, a deacetylase inhibitor, used so far in the treatment of lymphoma, has proven to unmask the dormant HIV virus. HIV infected cells are T helper cells or CD4 + cells. After the primary infection, HIV escapes immune defenses and the infection persists in the body. Lymph nodes are the sites where the virus replicates the most. It is during the asymptomatic infection, when the number of T helper cells remains normal. The symptomatic phase is next, and because of the massive replication of the virus, there is constant  decrease in T helper cells. A hallmark of HIV infection  is that the virus hides in some reservoirs, which are not accessible to antiretroviral drugs or immune response. These reservoirs are found in lymphoid organs, central nervous system, etc.. Healing can not occur because the virus is stuck in these reservoirs and can not be destroyed. There are, of course, other mechanisms by which the virus can not be destroyed by drugs, such as genomic variability.

Currently, treatment of HIV  is based on antiretroviral drugs, which are grouped into several classes: viral reverse transcriptase inhibitors, protease inhibitors, fusion inhibitors, and combined drugs. Viral reverse transcriptase inhibitors are divided into nucleoside analogues (NIRT) and nonnucleosides analogues (NNIRT). Combined treatment of HIV drugs can be made of the same class or different classes. The combination of different classes of drugs is called HAART, highly active antiretroviral therapy. HAART lowers viral load rapidly but this rapid response is followed by a slower decline over the next years. However, the disease can not be eradicated because of persistent virus in tissue reservoirs.
The new drug that has proven useful in the treatment of HIV infection, vorinostat, is used for treatment of cutaneous T cell lymphoma. It also appears that vorinostat is effective in treating recurrent glioblastoma multiforme and small cell lung cancer.

According to the study published July 25 in the scientific journal Nature, the administration of vorinostat in patients with HIV increases the levels of HIV RNA in CD4 + T cells, which means that this drug help unmask the virus responsible for persistent infection. After having conducted analyses in 8 patients infected with HIV, the researchers then administered vorinostat to these patients. After these investigations it was found that vorinostat increased levels of HIV RNA 4.5 times in CD4 + T cells. David Margolis, MD, professor of medicine, microbiology and immunology, and epidemiology at the University of North Carolina at Chapel Hill, said that this work is a new strategy to fight against latent HIV infection.

Parkinson Disease

Parkinson disease is a progressive degenerative disease that was first described in 1817 by the English neurologist James Parkinson, who named it agitated paralysis. Parkinson disease is a idiopathic neurological disorder.

Disease onset usually occurs between 50 and 65 and affects 1% of the population older than 60 years and over 6% of the population aged between 74 and 80 years. Parkinson disease is more common in men, sex ration being 1.5/1 for males . Onset before age of 40 years is very rare. Parkinson disease incidence is 200 cases per 100,000 inhabitants and has a lower frequency in Asia and Africa.

Parkinson Disease Pathophysiology

Major anatamopathologic aspect of Parkinson disease consists in the disappearance of pigmented dopaminergic neurons in substantia nigra (pars compact), especially in the ventro-lateral part which projects into the putamen. On section, this structure appears pale and depigmented. The normal concentration of dopamine in the putamen and caudate nucleus, the so-called neo-striatum dopaminergic pathway, is decreased by approximately 80% in Parkinson disease, which underlies dopamine precursors therapy. Approximately 60% -80% of dopaminergic neurons are lost before the clinical onset of symptoms.

Parkinson Disease

In the remaining pigmented neurons are highlighted eosinophilic cytoplasmatic inclusions called Lewy bodies, which are considered by some authors the histological markers of Parkinson disease. However, Lewy bodies are not pathognomonic for Parkinson disease, because, beside the fact that Lewy bodies are found in all cases of Parkinson disease, they also occur in elderly individuals who do not have Parkinson disease and can be considered as a presymptomatic phase of the disease. Lewy bodies may also occur in postencephalitic parkinsonism, in some cases of Parkinson-plus syndrome or other rare diseases such as Hallervorden-Spatz disease. In cases of Parkinson disease associated with dementia, Lewy bodies were highlighted in the cortex (dementia with Lewy bodies). Lewy bodies contain alpha-synuclein, a protein found in the synaptic gap, and phosphorylated neurofilaments, phospholipids and cytoskeleton elements, different from Pick bodies and neurofilaments found in Alzheimer’s disease. The cause of substantia nigra cellular degeneration is not known.

Parkinson disease is not a disease that affects only the dopaminergic pathways, many other structures being depopulated. Thus, locus ceruleus, the main source of nonadrenergic innervation of the central nervous system and dorsal motor nucleus of the vagus nerve are usually depopulated. Lesions are found in nonpigmented cell groups of Meynert nucleus, which is the main source of cholinergic innervation of the neocortex, as well as in the unnamed substance, hypothalamus, mammillary bodies, the midbrain reticular formation and raphe dorsal nucleus (serotonergic innervation source). Injuries were also found in intermediolateral tract of the spinal cord (the origin of sympathetic fibers) and sympathetic ganglia. These disseminated lesions show that Parkinson disease is a multisystemic neurological disorder.

Parkinson Disease Causes

The exact cause of Parkinson disease is still unknown, but is hypothesized that most cases are the result of a combination between genetic and environmental factors.

Parkinson Disease

Among the environmental factors that may be involved in development of Parkinson disease are mentioned:

• Pesticides, rural life, exposure to herbicides and proximity to industrial plants;
• In some cases was observed the development of parkinsonism similar to Parkinson disease, after self-injection of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridina), similar to chemical pesticides and herbicides. After exposure to this substance patients developed bradykinesia, rigidity and tremor, which improved after administration of dopamine precursors. It was assumed that some environmental toxin, similar to MPTP, could cause Parkinson disease, but until now no specific agent was identified;
• The oxidative hypothesis states that free radicals resulting from oxidative metabolism of dopamine have a role in the development of Parkinson disease.

Heredity is not a major factor in the development of Parkinson disease, but researches suggest that genetic factors are very important when disease begins after age 50 years. In a small group of patients with Parkinson disease were noted mutation of alpha-synuclein gene, called PD1. These individuals were characterized by early age of disease onset (mean age 47.5 years), rapid progression (mean age at death  56.1 years), lack of tremor, and good response to dopamine precursors therapy.

Syringomyelia

Syringomyelia is a chronic, progressive, degenerative disease of the spinal cord, characterized by the presence of a cystic degeneration (a cavity called syrinx) in the center of the spinal cord. Clinically, syringomyelia presents as main symptoms brachial muscle atrophy and dissociated sensory loss. The cavity is usually present in the cervical spine, but it can spread to the bulb, more rare to the pons or can extend to thoracic and lumbar segments of the spinal cord.

The exact cause of the disease is still unclear, but is assumed to be the result of incomplete closure of embryonic central canal, syringomyelia being included in the concept of status disraphicus. This hypothesis is supported by association of syringomyelia with other dysraphism aspects such as spina bifida, meningocele, myelomeningocele or chest malformations.

Another hypothesis sustain that the syrinx is the result of increased cerebrospinal fluid pressure due to delayed opening of Luscka and Magendie orifices of the fourth ventricle or due to the presence of obstructive factors near the foramen magnum, such as the herniation of cerebral tonsils (in Arnold -Chiari malformation).

Syringomyelia

Syringomyelia Symptoms

The disease occurs predominantly in men aged between 25 and 40 years. Rarely, clinical manifestations occur in childhood or adolescence. Syringomyelia onset is usually insidious, patient presenting painless burns of the arm or hand muscle atrophies are present.

Neurological impairment consist of a sensory lesional syndrome and a motor lesional syndrome. Sensory lesional syndrome consists of a characteristic sensory impairment called dissociated sensory loss, in which pain and temperature sensibility sensations are lost, while light touch, vibration, and position senses are preserved. Pain and temperature sensation may be impaired in either or both arms, or in a shawllike distribution across the shoulders and upper torso anteriorly and posteriorly. Due to the fact that sensory root of cranial nerve V (trigeminal) descends in the cervical region of the spinal cord, facial sensory impairment may be present.

Sensory lesional syndrome is produced by the anterior expansion of syrinx, interrupting the decussating spinothalamic fibers that mediate pain and temperature sensibility, resulting in loss of these sensations in radicular bands characteristic for injured neuromeres.

Syrinx extension into the anterior horns of the spinal cord cause motor lesional syndrome, characterized by damages of motor neurons (lower motor neuron), leading to diffuse muscle atrophy that begins in the hands, conferring different aspects of the hand and progresses proximally including the forearms and shoulder girdles. Particular aspects of the hand are:

• Simian hand, when the thumb goes in the same plan with the rest of the fingers, caused by atrophies that affect muscle from thenar and hypothenar eminence;
• Claw hand, when first phalanges are in hyperextension and the rest of the phalanges are in flexion, caused by muscle atrophies that affect interossei and lumbrical muscles;
• Preacher hand- hand remain in extension, due to long and deep flexors atrophies;
• Skeletal hand, when atrophies affect all muscle groups, including extensors.

Trophic disturbances occur frequently and are represented by painless ulcers of the hand and osteolytic painless arthropathy, most commonly in the shoulder. Hypertrophy of  the hand, is characteristic for syringomyelia and is called cheiromegaly.

When the cavity enlarges and involve the posterior columns of spinal cord, position and vibration senses in the feet are lost and astereognosis may be noted in the hands. Horner syndrome may also appear, caused by impairment of sympathetic neurons in the intermediolateral cell column.

Syrinx may extend from medulla to the cerebral bulb, causing syringobulbia.  Syringobulbia, sometimes may precede spinal cord damage. The bulbar symptoms are unilateral and consist of dysphagia, dysphonia, dysarthria, nystagmus, pharyngeal and palatal weakness, vocal cord paralysis, asymmetric weakness and atrophy of the tongue, and sensory loss involving primarily pain and temperature senses in the distribution of the trigeminal nerve. Rearly, may occur diplopia (double vision), vertigo and pain in the trigeminal nerve territory.

Syringomyelia Diagnosis

The initial evaluation of a patient suspected of having syringomyelia includes a comprehensive history and physical examination, because information obtained from physical examination will guide the imaging studies which are the paraclinical examinations that establish an accurate diagnosis.

Imaging studies include plain radiography which is not useful in highlighting the cavity, but can detect cervical canal dilation and cranio-vertebral anomalies that may be associated with syringomyelia.

CT with contrast is useful in diagnosis because it can demonstrate the presence of syrinx.

Magnetic resonance imaging (MRI) of the brain and spinal cord, performed in the sagittal plane, highlight with high accurcy the medullary cavity and the associated anomalies.

Syringomyelia MRI

Syringomyelia Treatment

New Study Manages To Prevent Neuroblastoma Resistance To Crizotinib

Researchers have discovered a new therapeutic combination to prevent resistance of neuroblastoma to crizotinib. Researchers work at The Institute of Cancer Research in London on neuroblastoma treatment was succesful. The study, led by The Institute of Cancer Research in collaboration with the Dana-Farber Cancer Institute and Children’s Hospital in Boston, shows that the new combination therapy had positive results in the first stage of trial.

Neuroblastoma, along with nephroblastoma, is one of the most solid solid tumors of child. Neuroblastoma derives from cells which originate in neural crest. Neuroblast cells  are cells that develop peripheral sympathetic ganglion neurons. It must be said that neuroblastoma is the most common malignant tumor diagnosed in the first month. Depending on the genetic component (n-myc), there are forms of neuroblastoma more aggressive or less aggressive. Symptoms caused by neuroblastoma differ depending on where the tumor size, extension, etc.. The most common sign is the  increase of abdomen. On palpation, the tumor shows features of a malignant tumor: firm, irregular surface, reinforcing the deep plans. Depending on the extension, neuroblastoma can cause spinal cord compression with neurological manifestation. In case of metastasis, the child may have hepatomegaly. Metastases may be present not only in the liver, but the eye or skin. Also, if the adrenal gland is involved, catecholamines secreted will cause hypertension. An important role is played by imaging diagnosis (MRI or CT) and exploration biochemical (urinary excretion of vanilla mandelic acid, metabolite of catecholamines).

Crizotinib Pills

Researchers have tried to prevent the emergence of resistance of  neuroblastoma by combining mTOR inhibitors with crizotinib. Crizotinib is a drug used to treat non-small cell Lung Carcinoma (NSCLC), approved by the FDA. It acts as ALK (anaplastic lymphoma kinase) and ROS1 (c-ros oncogene1, receptor tyrosine kinase) inhibitor. Although the cancer initially respond to crizotinib, subsequently ALK mutations occur in cancer cells and they become  resistant to treatment.

Now, due to combination with mTOR inhibitors crizotinib, researchers have found a solution to prevent the occurrence of cancer resistance. They hope that this combination therapy proved to be useful in other cancers, not only for neuroblastoma. mTOR (mammalian target of rapamycin (mTOR) protein kinase is actually a kinase protein rsponsible for cell division, transcription, cell motility and protein synthesis. Triggering PI3K/AKT/mTOR pathway is involved in the development of certain cancers, neuroblastoma, but also in certain adult cancers
After discovery, the researchers realized that neuroblastoma becomes resistant to crizotinib  by turning on the PI3K/AKT/mTOR pathway. Therefore, by inhibiting mTOR researchers could overcome the  tumor resistance to crizotinib.

Gene Responsible For Melanoma Discovered And Successfully Inhibited By University of Zurich Researchers

Researchers at the University of Zurich identified cancer stem cells as a new target in treating an aggressive form of skin cancer – malignant melanoma.

A team of stem-cell researchers from the University of Zurich was able to inhibit gene Sox 10 and thus prevent tumor growth and proliferation. Sox 10 gene is the gene that coordinates embryonic development and the fate of cell. According to latest research, a tumor is formed by a group of malignant stem cells and other less aggressive cells. Cancer stem cells are similar to normal stem cells except that these malignant cells are tumorigenic,  and lead to uncontrolled cell proliferation. In addition, they self-renew and differentiate in numerous cell types. These cells persist in tumors as distinct populations, which explains the process of metastasis and tumor recurrence.

Discussions on the idea that stem cells start tumors are still under debate. It is not  yet clear whether tumors derive from stem cells that have lost the property to proliferate or from cells that have acquired the capacity to regenerate. In addition, within a malignant tumor cells exhibit numerous abnormalities of structure. We already know that cancer cells present alterations in the nucleus,  the amount of cytoplasm is decreased, cells change their shape and function and so on.

Malignant Melanoma

Therefore, researchers at the University of Zurich have thought that by inhibiting cells that coordinate the entire cell growth (ie cancer stem cells) can stop tumor growth. During the study of several biopsies taken from patients with melanoma, the researchers found that one gene is highly active, that is Sox-10 gene, responsible for stem cell survival and cell division. Subsequently, researchers have tried to inhibit melanoma growth in mice by inhibiting Sox 10. And the result was positive. Future studies will confirm whether this finding applies to humans.

Melanoma is an aggressive form of skin cancer that develops from melanocytes, cells responsible for producing melanin, the pigment that gives skin color. It is responsible for 75% of deaths caused by skin cancers.  One important risk factor is ultraviolet radiation. Therefore the most common localizations of melanoma are back-in men, and legs-i women. Ultraviolet radiation alters the DNA of cells with the appearance of mutations. If the mutation affects protooncogenes or tumor suppressor genes, such as p53 gene (also called “genome guardian”), the cells begin to divide uncontrollably, leading to cancer. Currently, treatment of melanoma consists os tumor resection and adjuvant therapy such as chemotherapy, radiotherapy or immunotherapy.

Miller-Fisher Syndrome – Symptoms, Diagnosis And Treatment

Miller-Fisher syndrome is a variant of Guillain-Barre syndrome, characterized by ophthalmoplegia, ataxia and areflexia. These clinical signs can overlap with other signs and symptoms of Guillain-Barre syndrome.

Although it is assumed that Miller-Fisher syndrome is idiopathic, it was observed that this disease can develop after a recent viral, bacterial or mycoplasma infections and after vaccinations. Association with Campylobacter jejuni infection was also mentioned . In Japan have also been reported  cases of Miller-Fisher syndrome in the same family, suggesting a genetic predisposition for this disease. Miller-Fosher syndrome occurs  in both sexes, with a slight predominance in males.

Miller-Fisher Syndrome Symptoms

Clinically, symptomatic triad consisting of ophthalmoplegia, ataxia and areflexia is characteristic for this syndrome.

Ophthalmoplegia tends to be complete, sometimes have been observed cases of internuclear ophthalmoplegia and Parinaud syndrome (a group of abnormalities of eye movement and pupil dysfunction). Palpebral ptosis is also present and may be unilateral or bilateral, symmetrical or asymmetrical, complete or incomplete. Pupillary disturbances occur in over 50% of cases of Miller-Fisher syndrome and are characterized by reduction of pupillary reaction to light, accommodation disorders and anisocoria (unequal size of the pupils).

Miller-Fisher Syndrome Symptoms

Ataxia is a result of peripheral non-myelinated spinocerebellar fibers conduction disturbances , being a truncal ataxia.

Have been reported cases of Miller-Fisher syndrome associated with retrobulbar optic neuritis and accompanied by vision loss, with complete or incomplete vision recovery.

Cranial nerve impairment occurs, especially of the facial nerve, causing facial paralysis which can be unilateral or bilateral. Other cranial nerves which can be affected are ophthalmic branch of cranial nerve V (trigeminal nerve) and cranial nerve VIII (acoustic). Cranial nerves II (optic) and III (oculomotor) are less affected in this disease.

A characteristic of Miller-Fisher syndrome is the occurrence of migratory paresthesias, which are not usually accompanied by sensitive deficits. Sometimes, cases of sensitive ataxia have been reported.

Neurological disorders  in Miller-Fisher syndrome affects, in most cases, the peripheral nervous system. In some patients were reported impairments of central nervous system, accompanied by dysarthria, nystagmus, ataxic gait, ophthalmoparesis, pronounced tendon reflexes and positive Babinski sign). In some cases distinction between Miller-Fisher syndrome and brainstem encephalitis is very difficult.

Miller-Fisher Syndrome Diagnosis

Miller Fisher syndrome is diagnosed based on symptomatic triad consisting of ophthalmoplegia, ataxia and areflexia and parclinical examinations.

Serological tests reveal the presence of antibodies directed against certain gangliosides. It seems that anti-GQ1b antibody, of  IgG type correlates with ophthalmoplegia in Guillain-Barre syndrome and may correlate with ophthalmoplegia appeared in Miller-Fisher syndrome. In one case of Miller-Fisher syndrome were detected anti-cerebellar antibodies. Miller-Fisher syndrome patients present changes in cebrospinal fluid identical to those of Guillain-Barre syndrome (increased protein concentration over 400 mg / dl, but a normal cellularity, anomaly called albuminocytological dissociation).

Electrophysiological tests are abnormal in most cases and advocates for peripheral nerve dysfunction (electromyography, nerve conduction,  F waves, visual evoked potentials, sensory evoked potentials and auditory brain stem evoked potentials). Nerve biopsy reveal demyelination associated with axonal degeneration.

Neuroimagistically, ophthalmoparesis was confirmed by peripheral lesions of oculomotor nerve.

Miller-Fisher Syndrome

Miller-Fisher Syndrome Treatment

In most patients with Miller-Fisher syndrome spontaneous remission occurs after a period of 8-12 weeks of evolution, without treatment. Relapses are possible, but  are not characteristic for the disease. Some cases with severe evolution, require mechanical ventilation. In severe forms of disease plasmapheresis is useful. Intravenous administration of immunoglobulin, in doses of 400 mg / kg / day for a period of 5 days was shown to be effective.

Currently, the problem of concomitant impairment of central nervous system, supported by some authors, remains an open controversy for the following research. Are taken into account two alternatives: either the Miller-Fisher syndrome is a single entity caused by inflammatory and demyelinating lesions, located both in the peripheral nervous system and central nervous system; either the syndrome is caused by different pathological processes, some of which only affect the central nervous system, others affect only peripheral nervous system and others affect both the central nervous system and peripheral nervous system.

New Vaccine Prevents Weight Gain And Stimulates Weight Loss

In their effort to combat obesity, researchers have discovered a vaccine that prevents weight gain and stimulates weight loss. According to a study published in the Journal of Animal Science and Biotechnology, the researchers were able to induce weight loss following the administration of two vaccinations based on  somatostatin , JH17 and JH18, in mice.
Somatostatin, hormone known as GHIH, is an inhibitor of growth hormone. Growth hormone is an anabolic peptide hormone that stimulates not only growth, cell reproduction and regeneration, but also increases metabolism and therefore promotes weight loss. Researchers have thought that by injecting somatostatin, the body will react and produce antibodies against somatostatin, therefore the inhibitory action of somatostatin on growth hormone will be canceled. Consequently, growth hormone will increase the metabolism without being inhibited by somatostatin. Besides stimulating lipolysis, growth hormone has a role in stimulating protein synthesis, muscle growth and bone mineralization.

Vaccine

Researchers conducted the study on two groups of mice: one group consisting of 10 mice with induced-obesity and the control group. The group of obese mice received two vaccinations of modified somatostatin (first vaccine in the first day of the study and the second – study day 22). The control group received saline injections. Obese mice were fed a high fat diet eight weeks before the study and six weeks during the study. After 4 days from the first vaccine,  researchers found a decrease of 10% of body weight among obese mice, observation that was not noted in the control group. At the end of the study scientists observed that the vaccines caused the appearance of anti-somatostatin antibodies and a reduction in weight by 10%. It should be noted that researchers used a modified form of somatostatin that has not influenced the level or activity of insulin-like growth factor (IGF-1) or insulin.

Only time will tell if this vaccine will have similar results in humans. The idea of such a vaccine against obesity is not completely new. Not so long ago, researchers created a vaccine based on ghrelin, a hormone with a role in appetite control. Ghrelin stimulates fat storage for energy. Researchers have thought that by suppressing ghrelin, fatty deposits will be destroyed. The idea was based on immune stimulation and anti-ghrelin antibody production.

Obesity is one of the most important problems of the modern society. It is already known that obesity is associated with various cardiovascular diseases, type 2 diabetes and certain types of cancer. Despite researchers attempts to discover a vaccine against obesity, at present the only successful therapy for weight loss is based on diet, sports and some surgical interventions.

Emery-Dreifuss Muscular Dystrophy

First described in 1900 and then considered  the benign form of Duchenne muscular dystrophy, Emery-Dreifuss disease becomes a distinct clinical entity in 1966. So far, have been described two forms of Emery-Dreifuss muscular dystrophy: a X-linked recessive form and an autosomal dominant form.

X-linked recessive form occurs through a genetic mutation that consists of total absence of emerin, a muscle protein. Emerin is a nuclear membrane protein that is found mainly in skeletal muscle and cardiac muscle, but also in other tissues such as skin, colon, testes, ovaries and pancreas. The exact role of this protein is not fully understood, but is considered to participate in stabilizing the nuclear membrane against mechanical stress during muscle contraction. X-linked form of the disease affects mainly males.

Emery-Dreifuss Muscular Dystrophy

Autosomal dominant form appears through a genetic defect located on chromosome 1. Affected gene encodes a series of proteins called lamins A and C. These proteins are intermediate filaments found in the inner nuclear membrane and nucleoplasm of almost all cells of the body. Lamins have complex functions because they are providing mechanical strength to the nucleus, are involved in the determination of nuclear shape, and in the process of anchoring and spacing nuclear pore complexes. Lamins A and C possess an essential role in DNA replication and mRNA (mitochondrial RNA) transcription. This form of the disease is associated  with dilated cardiomyopathy and rhythm disturbances, most frequent arrhythmia being atrionentricular block . This form of Emery-Dreifuss myopathy affects both sexes equally.

Emery-Dreifuss Muscular Dystrophy Symptoms

Onset in X-linked form can occur at any stage of life, starting with the neonatal period, until the third decade of life. Emery-Dreifuss myopathy usually begins in adolescence. The most common signs are the appearance of muscle contracture and muscle weakness. Cardiac damage occurs much later, after striated muscle was affected and occurs most commonly around the age of 40 years.

The disease is characterized by a symptomatic triad:

• Muscle weakness and wasting in a scapulohumeroperoneal distribution;
• Early contractures of the elbow, ankle, and posterior neck;
• Cardiac conduction defects, cardiomyopathy, or both.

Contractures of the elbow and the cervical spine are suggestive for the disease  and later in evolution entire spine is affected causing stiffness. Peroneal muscle damage will lead to toe walking. Brachial biceps and triceps are affected in early stages of the disease.

Emery-Dreifuss Muscular Dystrophy Symptoms

Cardiac damage usually occurs in the second or third decade of life and is characterized by:

• Usually begins after onset of weakness and manifests as syncope in the second or third decade of life;
• Sudden cardiac death may be the first sign of cardiac damage;
• Pacemakers are needed by the age of 30 years;
• Atrial paralysis, bradycardia, atrial arrhythmias (atrial fibrillation, atrial flutter), atrioventricular conduction defects and ventricular cardiomyopathy represent signs of cardiac damage;
• 10-20% of female carriers in X-linked form of the disease present atrial arrhythmias or conduction defects and need ECG monitoring, once a year to prevent sudden cardiac death.

Emery-Dreifuss Muscular Dystrophy Diagnosis

Serum creatine is moderately increased in this form of the disease, if are present values of 50-100 times higher than normal, the diagnosis should be reconsidered as Duchenne myopathy or facioscapulohumeral muscular dystrophy.

Electromyography shows diminished or absent spontaneous muscle activity and  motor units present an activity of short duration and low amplitude. It is important to examine the most affected muscles.

Muscle biopsy is characteristic for muscle diseases with excessive variations in the diameter of muscle fibers, muscle fibers are hypertrophied, central nuclei,  excessive interstitial fibrosis and necrotic muscle fibers undergoing regeneration. Immunohistochemical study using emerin antibodies confirm the diagnosis by showing no nuclear staining. However muscle biopsy should be correlated with clinical data.

Emery-Dreifuss Muscular Dystrophy – Muscle Biopsy

Emery-Dreifuss Muscular Dystrophy Treatment

Emery-Dreifuss muscular dystrophy has no specific treatment. Are recommended procedures that are maintaining muscle activity, skeletal abnormalities correction, scoliosis and muscle contractures correction.

Due to the fact that atrial conduction disturbances and sudden cardiac death are the most important complications of the disease, prevention and treatment are required by the following procedures:

• Patients with bradycardia should benefit from pacemaker implantation;
• Intra-atrial thrombus, cerebral embolization and cardiomyopathy may still occur even in patients with pacemaker and for this reason, prophylaxis of this complications is required;
• Patients with progressive and untreatable cardiomyopathy should undergo cardiac transplantation;
• Ventricular arrhythmias may occur in the disease evolution and for this reason a cardioverter-defibrillator should be inserted.

Orthopedic treatment is aimed to maintain patient mobility for as long as possible and is needed to correct or to prevent muscle contractures and to increase range of motion.

To ensure the best possible therapy for a patient with Emery-Dreifuss muscular dystrophy is needed a approach team that is including a neurologist, pulmonologist, cardiologist, orthopedic surgeon, physiatrist and a physical therapist.

Landouzy Dejerine Muscular Dystrophy

Landouzy Dejerine muscular dystrophy, also known as facioscapulohumeral dystrophy was first described by Landouzy and Dejerine in 1884. It is a genetic disease, with autosomal dominant transmission in 70% -90% of cases. The genetic defect is located on chromosome 4, but the gene or genes that are affected in facioscapulohumeral dystrophy are still unknown. Landouzy Dejerine muscular dystrophy affects both sexes and rarely has a recessive, X-linked transmission. It is estimated that facioscapulohumeral dystrophy is the third most common muscular dystrophy, affecting 1 in 20,000 persons.

 Landouzy Dejerine Muscular Dystrophy Symptoms

Onset usually occurs between the ages of 6 and 12 years, but sometimes it can occur at the age of 30 years, 95% of patients have signs of disease before the age of 20 years. Infantile onset is very rare. The disease is more common in males, but asymptomatic cases are more common in women. Approximately one third of cases are asymptomatic.

The disease has an insidious onset, a slow, progressive evolution and affects facial muscles, starting with orbicularis oculi, orbicularis oris and zygomaticus muscle. Initial symptoms of the disease may go unnoticed, but some symptoms are insidious installed, so that, some patients have difficulties in whistling or in drinking liquid through a straw, while other patients report that they can not properly close their eyes during sleep. Usually, muscle damage is asymmetrical.

Atrophy of facial muscles gives  a characteristic appearance, called myopathic mask, muscle atrophies later extend to the scapular-humeral belt, pelvic belt being spared.

Facioscapulohumeral Dystrophy

The patient presents a dull facies, without physiological folds produced by laughing or crying, eyelids can not be completely close during sleep, due to orbicularis oculi atrophy. By affecting the orbicularis oris and zygomaticus muscle, upper lip becomes proeminent.

It is characteristic transverse laughter: at the attempt of laughing, upper lip will be applied to dental arches and mouth corners are moving back, possible by affecting the zygomaticus muscle. Chewing is difficult, the patient is no longer able to whistle or drink liquid through a straw.

Scapular belt damage occurs later at 82% of symptomatic patients, atrophy extension  will affect scapular muscles, chest muscles, trapezius (neck is elongated) and paravertebral muscles. Deltoid is usually spared and atrophy expansion is selective for biceps and triceps muscles, realizing a carcatural aspect of Popeye, due to massive forearm and deltoid muscles, in contrast with atrophic biceps and triceps muscles.

In rare cases, patients present congenital absence of some muscles, especially of the pectoral muscles. In rare cases, muscle atrophy may spread to the legs, anterior tibial muscle being most often affected, while posterior calf muscles are not affected.

Cognitive functions are preserved, cardiac damage is rare and the disease has a slow evolution, sometimes with lasting remissions.

Landouzy Dejerine Muscular Dystrophy Diagnosis

Serum creatine kinase is increased, but in some cases may present normal values.

Nerve conduction velocity is normal.

Electromyography shows diminished or absent spontaneous muscle activity and  motor units present an activity of short duration and low amplitude. It is important to examine the most affected muscles, especially facial and scapular muscles.

Muscle biopsy shows variable aspects. This must be done from a symptomatic muscle or a muscle that is presenting electrophysiological changes. Changes seen in muscle biopsy are:

• Multifocal distribution;
• Fiber size variation with central nuclei;
• Endomysial connective tissue proliferation;
• Regenerating, moth-eaten fibers and muscle fibers undergoing phagocytosis;
• Isolated angular atrophic fibers;
• Rimmed vacuoles;
• Focal inflammation in perivascular and perimysial distributions;
• Muscle fibers expressing membrane attack complex;
• Muscle fibers expressing class 1 major histocompatibility antigen.

Landouzy-Dejerine-Muscular-Dystrophy

Landouzy Dejerine Muscular Dystrophy Treatment

There is no specific treatment for Landouzy Dejerine muscular dystrophy. It was noted that administration of beta-2 adrenergic agonists, albuterol, improves muscle strength through non-specific anabolic effects.

Administration of corticosteroids did not improve muscle strength.

Creatine monohydrate, folic acid and methionine supplementation and myostatin inhibition (MYO-29) have been used, but with no clinical benefits.

Physiokinetotherapy can be useful. It was observed that aerobic training may improve muscle performance.  A program that consist of twelve weeks of low-intensity aerobic exercises (on a cycle ergometer at a heart rate corresponding to a work intensity of 65% of maximum oxygen volume  for 35 minutes daily, 5 times a week, for a period of 4 weeks) can be useful in the treatment of this disease because it was observed that is improving the oxygen uptake and and patients did not present signs of muscle damage.

Evolution of the disease is slowly, progressive, atrophies will extend from facial muscle to scapular belt. Are also described forms with prolonged episodes of remission. Life expectancy of these patients is good. Possible complications of the disease are represented by retinal vasculopathy, hearing loss in 64% of patients, mental retardation in 40% of cases and epileptic seizures that occur more frequently in early-onset cases. Other complications may include hypertension, arrhythmias and dilated cardiomyopathy.