Discussion in usmle step 1 started by orthopod, may 24. A 42yearold man has an autoimmune disorder resulting in proximal muscle weakness of the lower extremities. Mar 16, 2016 myoclonic epilepsy with ragged red fibers merrf is a multisystem disorder characterized by myoclonus, which is often the first symptom, followed by generalized epilepsy, ataxia, weakness, and dementia. Myoclonic epilepsy with ragged red fibers genetic and rare. Colobomas affecting the iris, which result in a keyhole appearance of the pupil, generally do not lead to vision loss. My biggest frustration was the wording of the biopsy results abnormal accumulations of mitochondria. Red ragged fibers diseases of the mitochondria can be caused by defects in nuclear or mitochondrial dna and result in decreased energy availability for cell processes. Clinical and brain mr imaging features focusing on the. Let us continue with this case and the ragged red fibers observed in the myocardium, the heart muscle, of the deceased boy. We help our clients achieve their business goals by providing advertisingmedia with attractive medical content and unique solutions to reach their target groups. Strokelike episodes and ragged red fibers are the two biggest buzzwords for mitochondrial inheritance disease.
The merrf diagnostic criteria described in 1980 by fukuhara et al included as typical manifestations of the dis. New launch of test pirates downloads with nbme answers and explanations. Bhoompally, mohandas surath departmetns of pathology and neurology, nizams institute of medical sciences, hyderabad. Several fibers have no staining for cytochrome oxidase cox. Ragged red fibers definition of ragged red fibers by. Enzymehistochemical examination revealed a marked reduction in cox activity and numerous ragged red fibers. The acronym, merrf, or myoclonus epilepsy and ragged red fiber disease, represents one of the early mitochondrial syndromes, whose molecular genetic basis was first established in 1990 by shoffner and coworkers. When you are at mile 75 the race director says im going to arbitrarily make 50% of you start over but i havent decided which of you have to. Myoclonus epilepsy associated with raggedred fibers merrf. Course 1 nbmefirst aid questions and study guide quizlet. Oxidative enzyme stains nadhtr, sdh, cox are more sensitive to the presence of mitochondria, and will often show subsarcolemmal aggregates in the absence of ragged red fibers on trichrome stain. In most cases, the signs and symptoms of this disorder appear during childhood or adolescence. The deficiency may be isolated or may coexist with other respiratorychain enzyme defects.
Content outlines and sample items national board of. Cognitive functions in myoclonic epilepsy with ragged red fibres. The same fibers are also called ragged blue fibers because they show an intense, irregular staining with succinic dehydrogenase and nadh histochemical stains. Myoclonic epilepsy with ragged red fibers merrf is a multisystem disorder characterized by myoclonus, which is often the first symptom, followed by generalized epilepsy, ataxia, weakness, and dementia. Overlapping leigh syndromemyoclonic epilepsy with ragged. Muscle biopsy specimen from a patient with type ii glycogenosis acid maltase deficiency, pompes disease shows marked vacuolization of virtually all muscle fibers cryostat section, hematoxylineosin. About 1 in 4,000 children in the united states will develop mitochondrial disease by the age of 10 years. Ragged red fibres definition of ragged red fibres by.
On sdh, cox muscle fibers may be normal or have increased staining in normal biopsies virtually all fibers have staining for cox. A 46yearold man comes to the physician for a followup examination. You are winning a 50 mile race a 266 on nbme 18 with 1 mile to go, then the race director says lets actually make this a 100 mile race. Show full abstract ragged red fibers and cytochrome c oxidase negative fibers were present in muscle. Myoclonus epilepsy associated with raggedred fibers. It is associated with defects in the mitochondrial oxidative phosphorylation. Conventional brain mr imaging showed atrophy of the superior cerebellar peduncles and the cerebellum in all patients and brain stem atrophy in 2 patients. The biopsies from the tibialis anterior and quadriceps femoris muscles revealed fibers of normal size with no muscle fiber necrosis or ongoing regeneration. Those are two very different statements in my mind, lol. In the meantime, post any specific questions you have, and someone will answer them correctly. Biochemical investigation revealed elevated lactate, pyruvate, and. They are an occasional finding in a wide variety of muscle diseases and are particularly characteristic of mitochondrial.
We report 3 patients with myoclonic epilepsy with ragged red fibers merrf diagnosed by mitochondrial a8344g mutation. Myoclonic epilepsy with ragged red fibers genetic and. Serum studies show an increased lactate concentration. Merrf myoclonic epilepsy with ragged red fibers is a multisystem disorder characterized by myoclonus often the first symptom followed by generalized epilepsy, ataxia, weakness, and dementia. He had a generalized tonicclonic seizure 1 month ago. Founded in year 2000, red fiber has developed into a state of the art fabric mill, offering high quality fabrics using technologically advanced methods. He went on to develop cranial nerve palsy, myoclonus, generalized seizures, ataxia, recurrent pneumonia, and hypotension. Cerebellar ataxia was the first symptom in all patients. If you could please give me an explanation along with the answer. Which of the following metabolic processes is most likely impaired in this patient. Merrf myoclonus epilepsy with ragged red fibers syndrome is an extremely rare disorder that begins in childhood and affects the nervous system and skeletal muscle as well as other body systems. Because mitochondrial disorders contain many variations and subsets, some particular mitochondrial disorders are very rare. When muscle is stained with gomori trichrome, characteristic ragged red fibers are visible under the microscope.
In some cases we could find some ragged red fibers rrf which histochemically show a pronounced accumulation of lipids and mitochondria and single fiber defects of cytochromecoxidase. Pathogenic mutations in the mitochondrial trna lys may cause the merrf syndrome. Study 25 nbme random notes flashcards from geoffrey b. In our taiwan and china facilities, red fiber has invested over usd 30,000,000 in knitting, dyeing, setting and printing equipment. Physical examination shows weakness of the left lower extremity.
The disease is mater nally inherited as is the mtdna. Theyre missing pieces of tissue in structures that form the eye. Up to 4,000 children per year in the us are born with a type of mitochondrial disease. Coloboma is an eye abnormality that occurs before birth. It is extremely rare, and has varying degrees of expressivity owing to heteroplasmy.
Merrf syndrome, also known as myoclonus epilepsy with ragged red fibers is a very rare multisystem disorder, part of the mitochondrial encephalomyopathies cluster, due to mitochondrial abnormalities mutations in mitochondrial deoxyribonucleic acid that mainly affects the muscular and nervous systems and becomes symptomatic during childhood or adolescence, affecting patients in an unequal. This is the first reported case of a double point mutation m. The features of merrf vary widely among affected individuals, even among members of the same family. Merrf syndrome nord national organization for rare.
Background motor neuron diseases amyotrophic lateral sclerosis als and spinal muscular atrophy sma have been rarely associated with mitochondrial respiratory chain defects. Succinate dehydrogenase deficiency archives of pathology. An increase in lipid droplets and a slight proliferation of mitochondria in type i muscle fibers are correlated with the duration of fibromyalgia. Cognitive functions in myoclonic epilepsy with ragged red. For those who study mitochondrial disorders, one of the more common histological hallmarks of the disease process in mitochondrial disorders are ragged red fibers. Ragged red fibers are an important marker for mitochondrial disease.
Post gardasil heart failure, ragged red fibers and thiamine. Onset is usually in childhood, occurring after normal early development. May 04, 2015 a group from universidade federal do parana in brazil asked the question, when should merrf myoclonus epilepsy associated with raggedred fibers be the diagnosis, and identified some of the clinical and laboratory manifestations associated with merrf. Myoclonic epilepsy and ragged red fiber disease mer rf has been shown to fulfill all of the criteria for a mito chondrial dna mtdna mutation. Mitochondrial myopathies show ragged red fibers on muscle biopsy due to the accumulation of diseased mitochondria in the subsarcolemma of the muscle fiber. May 24, 2015 nbme is a bit outdated, so it will come after the others. Amyotrophic lateral sclerosis with raggedred fibers. The finding is commonly associated with slowly progressive weakness of the muscles of. Anytime you have a question with ragged red fibers or anything similar in the description, along with either msk or neuro or both symptoms you should be think mitochondrial disease, inherited from the mother only, and heteroplasmy. Merrf syndrome nord national organization for rare disorders. A 5yearold boy is brought to the physician by his mother because of a 3month history of headache, clumsiness, and fatigue. Electron microscopy shows clusters of large, irregular mitochondria with crystallike inclusions. Merrf syndrome affects different parts of the body, particularly the muscles and nervous system.
The signs and symptoms of this disorder appear at an early age, generally childhood or adolescence. Apr 20, 2015 video shows what ragged red fibers means. This irregular contour is due to peripherally located subsarcolemmal collections of mitochondria that appear red with trichrome stain. Histochemically, several fibers were cytochrome c oxidase cox. This annoyed me because the definition of ragged red fibers which im assuming was their intention is accumulations of abnormal mitochondria. We present the case of a 16yearold boy with a family history of epilepsy who presented with acute respiratory failure, limb weakness, diabetes mellitus, sinus tachycardia, lactic acidosis, and pneumonia. The resources on this site should not be used as a substitute for professional medical care or advice. Clinical and histological study of sixty patients with ragged red fibers sundaram challa, meena a. Histological examination of muscle specimen showed slight fiber size variability, some nuclear centralizations and several fiber splittings along with a consistent number n10 of ragged red fibers rrf.
When should merrf myoclonus epilepsy associated with. He works long hours daily as the head chef and owner of a restaurant. Common findings are hearing loss, short stature, optic atrophy, and cardiomyopathy with wolffparkinsonwhite wpw. The distinguishing feature in merrf is myoclonus, consisting of sudden, brief, jerking spasms that can affect the arms and legs or the entire body. Analysis of a calf muscle biopsy specimen obtained from the left lower extremity shows ragged red fibers. To evaluate the hypothesis that mitochondrial dysfunction may play a role in the pathogensis of aging and inclusion body myositis, we studied the frequency of ragged red fibers in muscle biopsy specimens from 15 young and old normal adults, and from 27 patients with inclusion body myositis, polymyositis, or dermatomyositis.
Histochemical, immunohistochemical, and singlefiber pcr analysis showed that ragged red fibers rrf are associated both with high levels of mutant mitochondrial genomes greater than 85% mutant mtdna and with a partial cytochrome c oxidase deficiency. Sep 07, 2018 home medterms medical dictionary az list ragged red fibers with cpeo definition medical definition of ragged red fibers with cpeo medical author. Mitochondrial myopathy an overview sciencedirect topics. Histochemical, immunohistochemical, and single fiber pcr analysis showed that ragged red fibers rrf are associated both with high levels of mutant mitochondrial genomes greater than 85% mutant mtdna and with a partial cytochrome c oxidase deficiency. For detailed clinical features, see molecular genetics inheritance. There were no central nuclei and no increase in interstitial connective tissue. But any time you see one of those two buzzwords, the answer is heteroplasmy or mitochondrial inheritance. Ragged red fiber cryostat section, gomori trichrome. Quizlet flashcards, activities and games help you improve your grades. A feature of several mitochondrial dna disorders in which a high proportion of the muscle fibres contain structurally and functionally abnormal mitochondria. Fibers called ragged red fibers are generally considered the morphological characteristic of mitochondrial encephalomyopathies. Case report open access polg1 mutations and stroke like.
Ragged red fibers in normal aging and inflammatory. A 70yearold man comes to the emergency department 30 minutes after the onset of weakness, nausea, and lower abdominal and back pain that radiates to the lower extremities. Ragged red fibers are a pathologic finding in which muscle fibers appear grossly ragged. He underwent coronary artery bypass grafting 3 weeks ago. These results suggest that alpershuttenlocher syndrome, at least in some patients, is a. Symptoms usually first appear in childhood or adolescence after normal early development. When should merrf myoclonus epilepsy associated with ragged. Learn vocabulary, terms, and more with flashcards, games, and other study tools. Ragged red fibers are rarely seen in mitochondrial myopathies, however, they are quite useful when present. Myoclonic epilepsy with ragged red fibers merrf is a disorder that affects many parts of the body, particularly the muscles and nervous system.
The histopathologic assessment of succinate dehydrogenase activity in muscle biopsies of patients with suspected mitochondrial myopathies has focused on the finding of increased staining, usually in ragged red fibers, rather than on reduced staining. The disease was so named because the patients all had myoclonus epilepsy and mitochondrialdysfunction wasfound uponmuscle biopsy2. Users with questions about a personal health condition should consult with a qualified healthcare professional. Ophthalmologic examination shows ptosis of the left eye and bilateral external ophthalmoplegia. Objectives to describe a patient with typical als and the finding of ragged red fibers in muscle biopsy. Lactic acidosis is highly indicative too, but can be confused with other disorders. Merrf syndrome or myoclonic epilepsy with ragged red fibers is a mitochondrial disease. In addition to their red color, the abnormal fibers are coarse and disorganized. When stained and examined under the microscope these fibres appear red and ragged.