Chihuahua (chief), a leader of the Chiricahua tribe of Apache Native Americans
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Muhammad ibn 'Ali ibn al-Layth was amir of the Saffarid amirate from 910 until 911.
Early in 910 Muhammad's brother, the Saffarid amir al-Layth b. 'Ali, led an army west towards Fars in an effort to wrest it from its ruler, the slave commander Sebük-eri. Since both al-Layth and another brother, al-Mu'addal, were participating in the campaign, Muhammad was left behind in the capital Zarang as al-Layth's representative. The campaign ended in disaster, with al-Layth being captured and sent to the Abbasid court at Baghdad; when news of this reached Zarang in early September, Muhammad was hailed as amir in the provinces still part of the amirate. To cement his power, he imprisoned al-Mu'addal, who had managed to avoid being captured by Sebük-eri and had returned to Sistan.
Shortly after his ascension, Muhammad was forced to deal with the Samanids under Ahmad, who had recently been given a caliphal diploma for Sistan and its subordinate territories in an effort to break the power of the Saffarids once and for all. In response to Ahmad building up his forces in Herat, Muhammad raised an army himself. Due to financial constraints, much of the army consisted of peasants. He headed north to the frontier and had some minor engagements with the Samanids in March of 911. However, he was eventually defeated and the peasant contingent fled, forcing him to abandon the expedition.
At this point Muhammad was persuaded by his advisors that he needed the support of al-Mu'addal, who was still in prison. Following his release, al-Mu'addal took control of Zarang, so Muhammad headed to Bust instead. Here a revolt due to excessive taxation by Saffarid authorities had started. It was led by an Ibrahim b. Yusuf-al'Arif, who declared his loyalty to the Samanids. An advance Saffarid army had difficulty putting down the revolt until Ibrahim suddenly disappeared in battle, allowing the Saffarids to retake control of Bust.
Muhammad shortly after entered Bust, but he himself used violently oppressive methods in a desperate attempt to raise money. As a result, the citizens of Bust grew hostile to the Saffarids, and when the Samanid Ahmad arrived before the city, they helped him take it. Muhammad fled but was soon captured and brought back to Bust. In response to the request of the caliph, Ahmad sent Muhammad to Baghdad. His capture, coupled with the surrender of al-Mu'addal to another Samanid army, allowed the Samanids to briefly take over Sistan.
Bosworth, C.E. The History of the Saffarids of Sistan and the Maliks of Nimruz (247/861 to 949/1542-3). Costa Mesa, California: Mazda Publishers, 1994.
Myotonic dystrophy affects more than 1 in 8,000 people worldwide.[1] While myotonic dystrophy can occur at any age, onset is typically in the 20s and 30s.[1] It is the most common form of muscular dystrophy that begins in adulthood.[1] It was first described in 1909, with the underlying cause of type 1 determined in 1992.[2]
Presentation of symptoms and signs varies considerably by form (DM1/DM2), severity and even unusual DM2 phenotypes. DM1 symptoms for DM2 include problems with executive function (e.g., organization, concentration, word-finding) and hypersomnia. Conduction abnormalities are more common in DM1 than DM2, but all people are advised to have an annual ECG. Both types are also associated with insulin resistance. Myotonic dystrophy may have a cortical cataract with a blue dot appearance, or a posterior subcapsular cataract.[4]
DM2 is generally milder than DM1, with generally fewer DM2 people requiring assistive devices than DM1 people.[citation needed] In addition, the severe congenital form that affects babies in DM1 has not been found in DM2 and the early onset of symptoms is rarely noted to appear in younger people in the medical literature.
Symptoms may appear at any time from infancy to adulthood. DM causes general weakness, usually beginning in the muscles of the hands, feet, neck, or face. It slowly progresses to involve other muscle groups, including the heart. DM affects a wide variety of other organ systems as well.
Myotonic dystrophy (DM) is an inherited disease. A severe form of DM, congenital myotonic dystrophy, may appear in newborns of mothers who have DM. Congenital myotonic dystrophy can also be inherited via the paternal gene, although it is said to be relatively rare. Congenital means that the condition is present from birth.
Histopathology of DM2. Muscle biopsy showing mild myopathic changes and grouping of atrophic fast fibres (type 2, highlighted). Immunohistochemical staining for type-1 ("slow") myosin
In DM1, there is an expansion of the cytosine-thymine-guanine (CTG) triplet repeat in the DMPK gene. Between 5 and 37 repeats is considered normal, while individuals with between 38 and 49 repeats are considered to have a pre-mutation and are at risk of having children with further expanded repeats and, therefore, symptomatic disease.[9] Individuals with greater than 50 repeats are almost invariably symptomatic, with some noted exceptions. Longer repeats are usually associated with earlier onset and more severe disease, a process known as anticipation.[citation needed]
DMPK alleles with greater than 37 repeats are unstable and additional trinucleotide repeats may be inserted during cell division in mitosis and meiosis. Consequently, the children of individuals with premutations or mutations inherit DMPK alleles which are longer than their parents and therefore are more likely to be affected or display an earlier onset and greater severity of the condition, a phenomenon known as anticipation. Repeat expansion is generally considered to be a consequence of the incorporation of additional bases as a result of strand slippage during either DNA replication or DNA repair synthesis.[10] Misalignments occurring during homologous recombinational repair, double-strand break repair or during other DNA repair processes likely contribute to trinucleotide repeat expansions in DM1.[10] Paternal transmission of the congenital form is uncommon (13%), possibly due to selection pressures against sperm with expanded repeats, but juvenile or adult onset is equally transmitted from either parent. Anticipation tends to be less severe than in cases of maternal inheritance.
The RNA from the expanded trinucleotide repeat region forms intranucleoplasmic hairpin loops due to the extensive hydrogen bonding between C-G base pairs, and it has been demonstrated that these sequester the splicing regulator MBNL1 to form distinctive foci.[11]
DM2 is caused by a defect of the CNBP gene on chromosome 3.[12] The specific defect is a repeat of the cytosine-cytosine-thymine-guanosine (CCTG) tetranucleotide in the CNBP gene.[12] As it involves the repeat of four nucleotides, it is not a trinucleotide repeat disorder, but rather a tetranucleotide repeat disorder.[13][14]
The repeat expansion for DM2 is much larger than for DM1, ranging from 75 to over 11,000 repeats.[12] Unlike in DM1, the size of the repeated DNA expansion in DM2 does not appear to make a difference in the age of onset or disease severity.[9] Anticipation appears to be less significant in DM2 and most current reviews only report mild anticipation as a feature of DM2.[citation needed]
The diagnosis of DM1 and DM2 can be difficult due to the large number of neuromuscular disorders, most of which are very rare. More than 40 neuromuscular disorders exist with close to 100 variants.[citation needed]
As a result, people with multiple symptoms that may be explained by a complex disorder such as DM1 or DM2 will generally be referred by their primary care physician to a neurologist for diagnosis. Depending on the presentation of symptoms, people may be referred to a number of medical specialists including cardiologists, ophthalmologists, endocrinologists, and rheumatologists. In addition, the clinical presentation is obscured by the degree of severity or the presence of unusual phenotypes.
The clinical presentation for both people with DM1 and DM2 commonly differs from the conception of the diseases held by many neurologists. Clinicians who are less familiar with the myotonic dystrophies may expect people with both forms to present with the more severe, classic symptoms of DM1. As a result, people may remain undiagnosed or be misdiagnosed. A useful clinical clue for diagnosis is the failure of spontaneous release of the hands following strong handshakes due to myotonia (delayed relaxation of muscles after contraction) which accompanies muscle weakness.
Though there is presently no cure for DM and management is currently symptom based, a precise diagnosis is still necessary to anticipate multiple other problems that may develop over time (e.g. cataracts). An accurate diagnosis is important to assist with appropriate medical monitoring and management of symptoms. In addition, genetic counseling should be made available to all people because of the high risk of transmission. Potentially serious anesthetic risks are important to note, so the presence of this disorder should be brought to the attention of all medical providers.
There are two main types of myotonic dystrophy. Type 1 (DM1), also known as Steinert disease, has a severe congenital form and a milder childhood-onset form as well as an adult-onset form.[15] This disease is most often in the facial muscles, levator palpebrae superioris, temporalis, sternocleidomastoids, distal muscles of the forearm, hand intrinsic muscles, and ankle dorsiflexors.[16] Type 2 (DM2), also known as proximal myotonic myopathy (PROMM), is rarer and generally manifests with milder signs and symptoms than DM1.[citation needed]
Other forms of myotonic dystrophy not associated with DM1 or DM2 genetic mutations have been described.[9] One case which was proposed as a candidate for the "DM3" label,[17] was later characterized as an unusual form of inclusion body myopathy associated with Paget's disease and frontotemporal dementia.[9][13][18]
Genetic tests, including prenatal testing, are available for both confirmed forms. Molecular testing is considered the gold standard of diagnosis.
Testing at pregnancy to determine whether an unborn child is affected is possible if genetic testing in a family has identified a DMPK mutation. This can be done at 10–12 weeks gestation by a procedure called chorionic villus sampling (CVS) that involves removing a tiny piece of the placenta and analyzing DNA from its cells. It can also be done by amniocentesis after 14 weeks gestation by removing a small amount of the amniotic fluid surrounding the baby and analyzing the cells in the fluid. Each of these procedures has a small risk of miscarriage associated with it and those who are interested in learning more should check with their doctor or genetic counselor. There is also another procedure called preimplantation diagnosis that allows a couple to have a child that is unaffected with the genetic condition in their family. This procedure is experimental and not widely available. Those interested in learning more about this procedure should check with their doctor or genetic counselor.
It is possible to test someone who is at risk for developing DM1 before they are showing symptoms to see whether they inherited an expanded trinucleotide repeat. This is called predictive testing. Predictive testing cannot determine the age of onset that someone will begin to have symptoms, or the course of the disease. If the child is not having symptoms, the testing is not possible with an exception of emancipated minors as a policy.
There is currently no cure for or treatment specific to myotonic dystrophy. Therefore, the focus is on managing the complications of the disease, particularly those relating to the cardiopulmonary system as these account for 70% of deaths due to DM1.[9] Pacemaker insertion may be required for individuals with cardiac conduction abnormalities. Improving the quality of life which can be measured using specific questionnaires[19] is also a main objective of the medical care. Central sleep apnea or obstructive sleep apnea may cause excessive daytime sleepiness, and these individuals should undergo a sleep study. Non-invasive ventilation may be offered if there is an abnormality. Otherwise, there is evidence for the use of modafinil as a central nervous system stimulant, although a Cochrane review has described the evidence thus far as inconclusive.[citation needed]
Some small studies have suggested that imipramine, clomipramine and taurine may be useful in the treatment of myotonia.[9] However, due to the weak evidence and potential side effects such as cardiac arrhythmias, these treatments are rarely used. A recent study in December 2015 showed that a common FDA approved antibiotic, Erythromycin reduced myotonia in mice.[20] Human studies are planned for erythromycin. Erythromycin has been used successfully in patients with gastric issues.[21]
Altered splicing of the muscle-specific chloride channel 1 (ClC-1) has been shown to cause the myotonic phenotype of DM1 and is reversible in mouse models using Morpholino antisense to modify splicing of ClC-1 mRNA.[22]
Combined strengthening and aerobic training at moderate intensity was deemed safe for individuals with neuromuscular diseases.[23] The combination was found to increase muscle strength.[24] Specifically, aerobic exercise via stationary bicycle with an ergometer was found to be safe and effective in improving fitness in people with DM1.[25] The strength training or aerobic exercise may promote muscle and cardiorespiratory function, while preventing further disuse atrophy.[26][needs update] Cardiovascular impairments and myotonic sensitivities to exercise and temperature necessitate close monitoring of people and educating people in self-monitoring during exercise via the Borg scale, heart rate monitors, and other physical exertion measurements.[27]
Muscular weakness of dorsiflexors (dorsiflexion) hinders the ability to clear the floor during the swing phase of gait and people may adopt a steppage gait pattern[27] or ankle-foot-orthotics may be indicated.[9] Factors such as hand function, skin integrity, and comfort must be assessed prior to prescription. Neck braces can also be prescribed for neck muscle weakness.[9]
Upper and lower limb weakness, visual impairments and myotonia may lead to the need for mobility aids and functional adaptive equipment such as buttonhooks and handled sponges for optimal hand function. If assistive devices and home adaptations are needed, physical therapists may refer on to occupational therapist(s) for further assessment.[9]
DM1 is the most common form of myotonic muscular dystrophy diagnosed in children, with a prevalence ranging from 1 per 100,000 in Japan to 3-15 per 100,000 in Europe.[9] The prevalence may be as high as 1 in 500 in regions such as Quebec, possibly due to the founder effect. In most populations, DM1 appears to be more common than DM2. However, recent studies suggest that type 2 may be as common as type 1 among people in Germany and Finland.[1]
The incidence of congenital myotonic dystrophy is thought to be about 1:20,000. DM occurs in about 1 per 7,000–8,000 people and has been described in people from all over the world.[citation needed] It affects males and females approximately equally. About 30,000 people in the United States are affected.
Myotonic dystrophy was first described by a German physician, Hans Gustav Wilhelm Steinert, who first published a series of 6 cases of the condition in 1909.[28] Isolated case reports of myotonia had been published previously, including reports by Frederick Eustace Batten and Hans Curschmann, and Type 1 myotonic dystrophy is therefore sometimes known as Curschmann-Batten-Steinert syndrome.[29] The underlying cause of type 1 Myotonic dystrophy was determined in 1992.[2]
^ abcdefghijkMeola, G; Cardani, R (April 2015). "Myotonic dystrophies: An update on clinical aspects, genetic, pathology, and molecular pathomechanisms". Biochimica et Biophysica Acta. 1852 (4): 594–606. doi:10.1016/j.bbadis.2014.05.019. PMID24882752.
^Klein, AF; Dastidar, S; Furling, D; Chuah, MK (2015). "Therapeutic Approaches for Dominant Muscle Diseases: Highlight on Myotonic Dystrophy". Current Gene Therapy. 15 (4): 329–37. doi:10.2174/1566523215666150630120537. PMID26122101.
^Yanoff, Myron; Jay S. Duker (2008). Ophthalmology (3rd ed.). Edinburgh: Mosby. p. 411. ISBN978-0323057516.
^Mahadevan M, Tsilfidis C, Sabourin L, Shutler G, Amemiya C, Jansen G, Neville C, Narang M, Barceló J, O'Hoy K (March 1992). "Myotonic dystrophy mutation: an unstable CTG repeat in the 3' untranslated region of the gene". Science. 255 (5049): 1253–5. Bibcode:1992Sci...255.1253M. doi:10.1126/science.1546325. PMID1546325.
^van der Ven PF, Jansen G, van Kuppevelt TH, Perryman MB, Lupa M, Dunne PW, ter Laak HJ, Jap PH, Veerkamp JH, Epstein HF (November 1993). "Myotonic dystrophy kinase is a component of neuromuscular junctions". Hum. Mol. Genet. 2 (11): 1889–94. doi:10.1093/hmg/2.11.1889. PMID8281152.
^Harley HG, Walsh KV, Rundle S, Brook JD, Sarfarazi M, Koch MC, Floyd JL, Harper PS, Shaw DJ (May 1991). "Localisation of the myotonic dystrophy locus to 19q13.2-19q13.3 and its relationship to twelve polymorphic loci on 19q". Hum. Genet. 87 (1): 73–80. doi:10.1007/BF01213096. PMID2037285.
^Bird, Thomas D. (1 January 1993). "Myotonic Dystrophy Type 1". GeneReviews. Archived from the original on 18 January 2017. Retrieved 9 May 2016.update 2015
^ abcdefghijTurner C, Hilton-Jones D (April 2010). "The myotonic dystrophies: diagnosis and management". J. Neurol. Neurosurg. Psychiatry. 81 (4): 358–67. doi:10.1136/jnnp.2008.158261. PMID20176601.
^Ho TH, Savkur RS, Poulos MG, Mancini MA, Swanson MS, Cooper TA (July 2005). "Colocalization of muscleblind with RNA foci is separable from mis-regulation of alternative splicing in myotonic dystrophy". J. Cell Sci. 118 (Pt 13): 2923–33. doi:10.1242/jcs.02404. PMID15961406.
^ abcDay JW, Ricker K, Jacobsen JF, Rasmussen LJ, Dick KA, Kress W, Schneider C, Koch MC, Beilman GJ, Harrison AR, Dalton JC, Ranum LP (February 2003). "Myotonic dystrophy type 2: molecular, diagnostic and clinical spectrum". Neurology. 60 (4): 657–64. doi:10.1001/archneur.60.5.657. PMID12601109.
^ abDalton, Joline C.; Ranum, Laura PW; Day, John W. (1993-01-01). Pagon, Roberta A.; Adam, Margaret P.; Ardinger, Holly H.; Wallace, Stephanie E.; Amemiya, Anne; Bean, Lora JH; Bird, Thomas D.; Fong, Chin-To; Mefford, Heather C. (eds.). Myotonic Dystrophy Type 2. Seattle (WA): University of Washington, Seattle. PMID20301639. Archived from the original on 2017-01-28.updated 2013
^Le Ber I, Martinez M, Campion D, Laquerrière A, Bétard C, Bassez G, Girard C, Saugier-Veber P, Raux G, Sergeant N, Magnier P, Maisonobe T, Eymard B, Duyckaerts C, Delacourte A, Frebourg T, Hannequin D (September 2004). "A non-DM1, non-DM2 multisystem myotonic disorder with frontotemporal dementia: phenotype and suggestive mapping of the DM3 locus to chromosome 15q21-24". Brain. 127 (Pt 9): 1979–92. doi:10.1093/brain/awh216. PMID15215218.
^Udd B, Meola G, Krahe R, Thornton C, Ranum LP, Bassez G, Kress W, Schoser B, Moxley R (June 2006). "140th ENMC International Workshop: Myotonic Dystrophy DM2/PROMM and other myotonic dystrophies with guidelines on management". Neuromuscul. Disord. 16 (6): 403–13. doi:10.1016/j.nmd.2006.03.010. PMID16684600.
^Dany A, Barbe C, Rapin A, Réveillère C, Hardouin JB, Morrone I, Wolak-Thierry A, Dramé M, Calmus A, Sacconi S, Bassez G, Tiffreau V, Richard I, Gallais B, Prigent H, Taiar R, Jolly D, Novella JL, Boyer FC (November 2015). "Construction of a Quality of Life Questionnaire for slowly progressive neuromuscular disease". Qual Life Res. 24 (11): 2615–23. doi:10.1007/s11136-015-1013-8. PMID26141500.
^Voet NB, van der Kooi EL, Riphagen II, Lindeman E, van Engelen BG, Geurts AC (July 2013). "Strength training and aerobic exercise training for muscle disease". Cochrane Database Syst Rev (7): CD003907. doi:10.1002/14651858.CD003907.pub4. hdl:2066/123481. PMID23835682.
^Cup EH, Pieterse AJ, Ten Broek-Pastoor JM, Munneke M, van Engelen BG, Hendricks HT, van der Wilt GJ, Oostendorp RA (November 2007). "Exercise therapy and other types of physical therapy for patients with neuromuscular diseases: a systematic review". Arch Phys Med Rehabil. 88 (11): 1452–64. doi:10.1016/j.apmr.2007.07.024. PMID17964887.
^Orngreen MC, Olsen DB, Vissing J (May 2005). "Aerobic training in patients with myotonic dystrophy type 1". Ann. Neurol. 57 (5): 754–7. doi:10.1002/ana.20460. PMID15852373.
^Voet NB, van der Kooi EL, Riphagen II, Lindeman E, van Engelen BG, Geurts AC (January 2010). "Strength training and aerobic exercise training for muscle disease". Cochrane Database Syst Rev (1): CD003907. doi:10.1002/14651858.CD003907.pub3. hdl:2066/123481. PMID20091552.
^Olbrych-Karpińska B, Tutaj A (September 1981). "[Case of Curschmann-Batten-Steinert syndrome]". Wiad. Lek. (in Polish). 34 (17): 1467–9. ISSN0043-5147. PMID7331343.
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