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NEUROPATHIES ASSOCIATED WITH SYSTEMIC DISORDER Diabetic Neuropathies. One of the most common complications of diabetes mellitus in western world is neuripathy.virtually every type of peripheral nerve fiber can b including sensory, autonomic, and motor nerve fibers. Therefore diabetic neuropa have diverse presentations. The term, diabetic neuropathy, includes all of these classification syste identifies all subtypes. Nonetheless, most diabeteic neurop classified as focal or multi focal neuropathies. Insience. Because of underrreporting and variations on diagnostic criteria, the exact prevalence of diabeteic neuropathiy is not known. However, it is clea number of people are affected by diabetic neuropathy. Over ! million "mericans diabetes, and this number increases by #$ each year. %eripheral neuropathy is a complication of diabetes, with #$ of patients already having diabeteic neuropath diabetes is diagnosed and up to #&$ of patients with diabetes ocer '# years have of neuropathy. (n one study, clinical symptom of diabetic neuropathy were presen sub*ects with diabtere and this number increased to !&,#$ when +uantitative neur examination and nerve conduction studies as described later- were used diagnosis. "nother study reported evidence of neuropathy in # $ of patients wit diabetes and in //$ of patients with type (( diabetes, and it is estimated that hospitali0ed patients with diabetes and '&$ of patients in the community with di neuropathy. Historically, the diagnosis of diabetic neuropathy depended primaril and symptoms. Now electrophysiological testing is used to diagnose cases where p is unclear. Etio!o"# an patho"enesis. Over the past '& years, research has helped to clarify t pathogenensis of diabetic neuropathy. However, the exact prcess that cause this still unclear, and it is difficult to combine the most popular theories into one explanation. These theories include thatnerve damage is caused by altered polyol metabolism, poor microvascular circulation, toxic glycosilation end1products, oxidative stress, low levels of neurothropic factors, and2or by excess of products of esse metabolism. (t is proposed that altered polyol metabolism cantributes to the development of neuropathy, polyol is a general term for sugar alcohol, which include glucose. 3 uptake of glucose by peripheral nerves is not insulin1dependant, when blood suga

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NEUROPATHIES ASSOCIATED WITH SYSTEMIC DISORDERDiabetic Neuropathies. One of the most common complications of diabetes mellitus in western world is neuripathy.virtually every type of peripheral nerve fiber can be affected, including sensory, autonomic, and motor nerve fibers. Therefore diabetic neuropathy can have diverse presentations. The term, diabetic neuropathy, includes all of these, and no single classification syste identifies all subtypes. Nonetheless, most diabeteic neuropathies can be classified as focal or multi focal neuropathies.Insidence. Because of underrreporting and variations on diagnostic criteria, the exact prevalence of diabeteic neuropathiy is not known. However, it is clear that a very large number of people are affected by diabetic neuropathy. Over 18 million Americans have diabetes, and this number increases by 5% each year. Peripheral neuropathy is a common complication of diabetes, with 5% of patients already having diabeteic neuropathy when their diabetes is diagnosed and up to 50% of patients with diabetes ocer 25 years have symptoms of neuropathy. In one study, clinical symptom of diabetic neuropathy were present in 32% of subjects with diabtere and this number increased to 80,5% when quantitative neurological examination and nerve conduction studies (as described later) were used to make the diagnosis. Another study reported evidence of neuropathy in 59% of patients with type I diabetes and in 66% of patients with type II diabetes, and it is estimated that 30% of hospitalized patients with diabetes and 20% of patients in the community with diabetes have neuropathy. Historically, the diagnosis of diabetic neuropathy depended primarily on signs and symptoms. Now electrophysiological testing is used to diagnose cases where presentation is unclear.Etiology and pathogenesis. Over the past 20 years, research has helped to clarify the pathogenensis of diabetic neuropathy. However, the exact prcess that cause this problem are still unclear, and it is difficult to combine the most popular theories into one consistent explanation. These theories include that nerve damage is caused by altered polyol metabolism, poor microvascular circulation, toxic glycosilation end-products, oxidative stress, low levels of neurothropic factors, and/or by excess of products of essential fatty acids metabolism.It is proposed that altered polyol metabolism cantributes to the development of diabetic neuropathy, polyol is a general term for sugar alcohol, which include glucose. Since the uptake of glucose by peripheral nerves is not insulin-dependant, when blood sugar levels are high, peripheral nerves take up a lot of glucose. This glucose is converted to sorbitol, and one theory is that the sorbitol exerts osmotic pressure, drawing fluid into the nerve, which causes swelling and damage. However recent research indicates that high concentration of sorbitol in nerves do not cause nerve damage and it may be that it is the high metabolic flux of glucose through the polyol pathway that damages the peripheral nerves.Alternatively, doabeteic neuropathy may be caused by microvascular ischemia. Diabetes is known to cause microvascular vasoconstriction and atherosclerosis, capilary basement membrane thickening, and endothelial cell hyperthropy. This in turn results in decreased endoneurial blood flow and diminished oxygen tension and hypoxia, which eventually lead to nerve damage and neuropathy.Reduced levels of nerves growth factor (NGF) in diabetes may also contribute to the development of diabetic neuropathy. NGF is neurotrophic factor that is similar to insulin in molecular, structural, and physiological properties. Low serum levels of NGF in patients with diabetes have been found to correlate with their degree of peripheral neuropathy. The formation of advanced glycosylation end products, oxidative stress, and protein kinase C may also affect the development of diabeteic neuropathy.Clinical presentation. Diabetic neuropathy most commonly present with distal symmetrical sensorimotor signs and symptom. Typically,the distribution follows a length-dependent pattern, with the most dista extremities (the toes) being involved first, followed by the feet and spreading up the legs in stocking distribution. The neuropathy may advance to involve the fingers, spreading up to the hands and forearms in a glove distribution. Later still, the trunk may be affected in an anterior wedge-shaped pattern. There are usually sensory changes and mild weakness of the ankle dorsiflexor and toe extensor muscles, accompanied by electromyographic (EMG) evidence of denervation. Distal muscle weakness and athropy can be profound in advance cases. Positive symptoms, such as paresthesias, burning, tingling, aching, cold sensation, lancinating (sharp) pain, or pain produced by normal touch (allodynia) pr by a change in temperature, are often reported. When there is pain, it is often worse at night. Negative signs and symptom, such as sensory loss, depression or absence of ankle jerks, and loss of vibratory sensation, are often present and may not be reported by patients but should be sought out with a thorough examination.Charcot arthropathy, also known as neuropathic arthropathy, is a condition that affects some diabetic patients about 8-10 years after the onset of sensory loss from peripheral neuropathy. Charcot arthropaty is caused by lack of pain sensation and proprioception that result i unnoticed injuries to joints, generally in the foot. Repeated small injuries, such as strains and even fractures tend to accur as the joint become more unstable until finally the joints are permanently destroyed and the foot becomes deformed. Sensory loss accompanied by vascular insufficiency is considered to be the primary cause of foot ulcer, which often result in amputations in patiens with diabetes. Sensorimotor plyneuropathy is present in 85% of patients with diabetes undergo amputation.The autonomic nerve involvement that commmonly accompanies diabetic sensorimotor plyneuropathy may also cause potural hypotension, impotence, bladder atony, gastroparesis and nocturnal diarrhea, postprandial sweating, and diminished distal limb sweating.HEREDITARY MOTOR AND SENSORY NEUROPATHIESCharcot-Marie-Tooth (CMT) disease. CMT disease is a clinically and genetically heterogenous group of inherited peripheral nerve disorders that can affect the sensory and/or the motor nerves. It usually presents with distal weakness and sensory loss that starts in the patients teens or twenties and progressed gradually over their life times.The first description of this syndrome from jean-martin Charcot and Pierre Marie of France, who in 1886 described a syndrome of progressive muscular atrophy of the feet and legs, followed by athropy of the hand and forearm muscles, tightness of achillesm tendons and pescavus, with the lower extremities resembling inverted champagne bottle. Shortly thereafter, Howard Henry Tooth of the united kingdom described a group if his patients with and inherited progressive symetrical athrophy of the distal muscle that began early in life and was caused by peripheral nerve dysfunction. More recently, CMT has been devided into different classifications of CMT.Incidence. In the united states, one in 2,500 peple are affected CMT, which makes it the most common inherited neurological disorder. The prevalence is 28.2 per 100.000 in spain. 17,5 per 100.000 in japan and 10.8 per 100000 in italy.Etiology and pathogenesis. CMT is caused by mutation in genes that produce proteins involved in the structured and function of either peripheral nerve axon or the myelin sheath, thus causing and axonal or demyelinating neuropathy.in CMT1A, a dmyelinating neuropathy that accounts for 80%of VMT1 and 70% of all CMT. Chromosome 17 undergoes gene mutation that alter proteins (PMP22) respnsible for myelin production by schwan cells in the peripheral nervous system. PMP22is overprooduced, leading t defective axon myelination. Histological examination reveals the presence of many thinly myelinated and remyelinatd nerve dibers, with multiple onion bulbs, more pronounced in the distal than proximal fibers. Typically the axon is present in the center of the onion bulb and the myelin sheath i thin or absent/In axonal neuropathies, such as CMT2, there is typically loss of myelinated, axonal atrophy and small clusters of thinly myelinatd of thinly myelinatid regenerating axons, myelin in the center of the onion club ath tye myelin sheath.Clinical presentation. CMT neuropathy affects both motor and sensory nerve fibers. Therefore patients with CMT typically present with distal muscle weakness or atrophy, strutural foot abnormalities, soft tissue complications, and EMG abnormalities. Furthermore, absen or diminished deep tendon reflexes and impaird sensation saensation are also present to varying degrees iri certain forms of CMT.findings are smiliar among affected family member.Generally, distal muscle weakness resuts in footdrop and steppage gait with frequent tripping or falls. Pes cavus and hammertoes, which are also common, are caused by weakness in the intrinsic foot muscle and the unequal action of the long toe flexors and extensor. Typically, few patients seek help suggesting that they experience few symptoms that they are accustomed to their symptoms and manage well functionally, or that they believe that no help is available.CMT symptoms usually present in second or third decade of life, ranging from infancy to mid-adulthood, depnding on the CMT subtype. Symptoms usually progress gradually and vary in severity. Some may have such mild symptoms that they do not notice, while other with severe form of the disorder may be severly compromised because of respiratory muscle involvement. CMT is rarely fatal, and most people who have disease have a normal life expactancy.

NEUROPATI TERKAIT DENGAN GANGGUAN SISTEMIKNeuropati diabetik. Salah satu komplikasi yang paling umum dari diabetes mellitus di dunia barat adalah neuripathy.virtually setiap jenis serat saraf perifer dapat dipengaruhi, termasuk serat sensorik, otonom, dan saraf motorik. Oleh karena itu neuropati diabetes dapat memiliki beragam presentasi. Istilah, neuropati diabetes, termasuk semua ini, dan tidak ada syste klasifikasi tunggal mengidentifikasi semua subtipe. Meskipun demikian, sebagian besar neuropati diabeteic dapat diklasifikasikan sebagai neuropati fokal fokus atau multi.Epdemiologi. Karena underreporting dan variasi pada kriteria diagnostik, prevalensi tepat neuropathiy diabeteic tidak diketahui. Namun, jelas bahwa jumlah yang sangat besar dari orang yang terkena neuropati diabetes. Lebih dari 18 juta orang Amerika menderita diabetes, dan jumlah ini meningkat sebesar 5% setiap tahun. Neuropati perifer adalah komplikasi umum dari diabetes, dengan 5% dari pasien yang sudah memiliki neuropati diabeteic ketika diabetes mereka didiagnosis dan sampai 50% dari pasien dengan diabetes ocer 25 tahun memiliki gejala neuropati. Dalam sebuah penelitian, gejala klinis neuropati diabetes hadir di 32% dari subyek dengan diabtese dan jumlah ini meningkat menjadi 80,5% saat pemeriksaan neurologis kuantitatif dan studi konduksi saraf (seperti yang dijelaskan kemudian) yang digunakan untuk membuat diagnosis. Studi lain melaporkan bukti neuropati di 59% dari pasien dengan diabetes tipe I dan 66% pasien dengan diabetes tipe II, dan diperkirakan bahwa 30% dari pasien rawat inap dengan diabetes dan 20% dari pasien di masyarakat dengan diabetes memiliki neuropati . Secara historis, diagnosis neuropati diabetes tergantung terutama pada tanda-tanda dan gejala. Sekarang pengujian elektrofisiologi digunakan untuk mendiagnosa kasus di mana presentasi tidak jelas.Etiologi dan patogenesis. Selama 20 tahun terakhir, penelitian telah membantu untuk mengklarifikasi pathogenensis neuropati diabetes. Namun, prosess tepat yang menyebabkan masalah ini masih belum jelas, dan sulit untuk menggabungkan teori yang paling populer menjadi satu penjelasan yang konsisten. Teori ini termasuk kerusakan saraf yang disebabkan oleh perubahan metabolisme poliol, sirkulasi mikrovaskular miskin, glikosilasi-produk akhir beracun, stres oksidatif, rendahnya tingkat faktor neurothropic, dan / atau kelebihan produk asam lemak esensial metabolisme.Diduga perubahan metabolisme poliol berpengaruh pada pengembangan neuropati diabetes, poliol adalah istilah umum untuk alkohol gula, yang meliputi glukosa. Karena penyerapan glukosa oleh saraf perifer tidak tergantung insulin-saat kadar gula darah yang tinggi, saraf perifer mengambil banyak glukosa. Glukosa ini diubah menjadi sorbitol, dan salah satu teori adalah bahwa sorbitol yang memberi tekanan osmotik, menarik cairan ke dalam saraf, yang menyebabkan pembengkakan dan kerusakan. Namun penelitian terbaru menunjukkan bahwa konsentrasi tinggi sorbitol di saraf tidak menyebabkan kerusakan saraf dan mungkin bahwa itu adalah fluks metabolik tinggi glukosa melalui jalur poliol yang merusak saraf perifer.Atau, neuropati doabeteic dapat disebabkan oleh iskemia mikrovaskuler. Diabetes diketahui menyebabkan vasokonstriksi mikrovaskuler dan aterosklerosis, Capilary membran basal penebalan, dan hyperthropy sel endotel. Hal ini pada gilirannya menghasilkan penurunan aliran darah endoneurial dan tekanan oksigen berkurang dan hipoksia, yang akhirnya menyebabkan kerusakan saraf dan neuropati.Menurunnya tingkat faktor pertumbuhan saraf (NGF) pada diabetes juga dapat berkontribusi terhadap perkembangan neuropati diabetes. NGF adalah faktor neurotropik yang mirip dengan insulin dalam sifat molekul, struktur, dan fisiologis. Kadar serum rendah NGF pada pasien dengan diabetes telah ditemukan berkorelasi dengan tingkat mereka neuropati perifer. Pembentukan produk canggih glikosilasi akhir, stres oksidatif, dan protein kinase C juga dapat mempengaruhi perkembangan neuropati diabeteic.Presentasi klinis. Neuropati diabetes paling sering hadir dengan tanda dan gejala sensorimotor simetris distal. Biasanya, distribusi mengikuti pola panjang-dengan ekstremitas yang paling distal (jari kaki) terlibat pertama, diikuti oleh kaki dan menyebar sampai kaki dalam distribusi stocking. Neuropati dapat melibatkan jari, menyebar sampai ke tangan dan lengan dalam distribusi sarung tangan. Kemudian mungkin akan terpengaruh dalam pola berbentuk baji anterior. Biasanya ada perubahan sensorik dan kelemahan ringan pergelangan kaki dorsiflexor dan kaki ekstensor otot, disertai dengan elektromiografi (EMG) bukti denervasi. Kelemahan otot distal dan athropy bisa mendalam dalam kasus muka. Gejala positif, seperti parestesia, terbakar, kesemutan, sakit, sensasi dingin, nyeri pedih (tajam) nyeri, atau nyeri yang dihasilkan oleh sentuhan yang normal (allodynia) pr oleh perubahan suhu, sering dilaporkan. Ketika ada rasa sakit, seringkali lebih buruk di malam hari. Tanda-tanda negatif dan gejala, seperti gangguan sensorik, depresi atau tidak adanya tersentak pergelangan kaki, dan hilangnya sensasi getaran, sering hadir dan tidak dapat dilaporkan oleh pasien tetapi harus dicari dengan pemeriksaan menyeluruh.Charcot arthropathy, juga dikenal sebagai arthropathy neuropatik, adalah suatu kondisi yang mempengaruhi beberapa pasien diabetes sekitar 8-10 tahun setelah onset gangguan sensorik dari neuropati perifer. Charcot arthropaty disebabkan oleh kurangnya sensasi rasa sakit dan proprioception yang mengakibatkan saya cedera tanpa disadari sendi, umumnya di kaki. Luka kecil berulang, seperti strain dan bahkan patah tulang cenderung accur sebagai sendi menjadi lebih tidak stabil hingga akhirnya sendi dihancurkan secara permanen dan kaki menjadi cacat. Gangguan sensorik disertai dengan insufisiensi vaskular dianggap menjadi penyebab utama dari ulkus kaki, yang sering mengakibatkan amputasi di penderita diabetes. Sensorimotor plyneuropathy hadir dalam 85% dari pasien dengan diabetes menjalani amputasi.Keterlibatan saraf otonom yang biasa menyertai diabetes sensorimotor plyneuropathy juga dapat menyebabkan hipotensi potural, impotensi, kandung kemih atonia, gastroparesis dan diare nokturnal, berkeringat postprandial, dan berkurang berkeringat ekstremitas distal.NEUROPATI SENSORIK DAN MOTORIK HEREDITERCharcot-Marie-Tooth (CMT) penyakit. Penyakit CMT adalah kelompok klinis dan genetik heterogen dari warisan gangguan saraf perifer yang dapat mempengaruhi sensorik dan / atau saraf motorik. Ini biasanya menyajikan dengan kelemahan distal dan gangguan sensorik yang dimulai pada pasien remaja atau dua puluhan dan berkembang secara bertahap selama masa hidup mereka.Deskripsi pertama sindrom ini dari jean-martin Charcot dan Pierre Marie Perancis, yang pada tahun 1886 menggambarkan sindrom atrofi otot progresif kaki dan kaki, diikuti oleh athropy dari tangan dan lengan bawah otot, sesak tendon achillesm dan pescavus, dengan ekstremitas bawah menyerupai botol sampanye terbalik. Tak lama kemudian, Howard Henry Tooth dari kerajaan bersatu dijelaskan kelompok jika pasien dengan dan mewarisi athrophy simetris progresif dari otot distal yang dimulai pada awal kehidupan dan disebabkan oleh disfungsi saraf perifer. Baru-baru ini, CMT telah dibagi ke dalam klasifikasi yang berbeda dari CMT.Kejadian. Di Amerika Serikat, satu di 2.500 peple dipengaruhi CMT, yang membuatnya gangguan neurologis yang paling umum yang diwariskan. Prevalensi adalah 28,2 per 100.000 di Spanyol. 17,5 per 100.000 di Jepang dan 10,8 per 100000 di Italia.Etiologi dan patogenesis. CMT disebabkan oleh mutasi pada gen yang memproduksi protein yang terlibat dalam terstruktur dan fungsi baik saraf akson perifer atau selubung mielin, sehingga menyebabkan dan aksonal atau demielinasi neuropathy.in CMT1A, neuropati dmyelinating yang menyumbang 80% dari VMT1 dan 70% semua CMT. Kromosom 17 mengalami mutasi gen yang mengubah protein (PMP22) respnsible untuk produksi myelin oleh sel Schwan dalam sistem saraf perifer. PMP22is overprooduced, memimpin t rusak akson mielinasi. Pemeriksaan histologi menunjukkan adanya banyak tipis myelinated dan remyelinatd dibers saraf, dengan beberapa lampu bawang, lebih jelas di distal dari serat proksimal. Biasanya akson hadir di tengah bola bawang dan selubung myelin i tipis atau tidak ada /Pada neuropati aksonal, seperti CMT2, ada biasanya kehilangan myelinated, atrofi aksonal dan kelompok kecil myelinatd tipis dari myelinatid tipis regenerasi akson, myelin di pusat klub bawang ath tye selubung mielin.Presentasi klinis. CMT neuropati mempengaruhi baik motorik dan serabut saraf sensorik. Oleh karena itu pasien dengan CMT biasanya hadir dengan kelemahan otot distal atau atrofi, kelainan kaki strutural, komplikasi jaringan lunak, dan kelainan EMG. Selanjutnya, absen atau berkurang refleks tendon dalam dan impaird sensasi saensation juga hadir untuk berbagai derajat IRI bentuk-bentuk tertentu dari CMT.findings yang smiliar antara anggota keluarga yang terkena dampak.Umumnya, kelemahan otot distal resuts di footdrop dan kiprah steppage dengan sering tersandung atau jatuh. Pes cavus dan hammertoe, yang juga umum, disebabkan oleh kelemahan otot kaki intrinsik dan tindakan yang tidak merata fleksor kaki panjang dan ekstensor. Biasanya, beberapa pasien mencari bantuan menunjukkan bahwa mereka mengalami beberapa gejala yang mereka terbiasa gejala mereka dan mengelola dengan baik fungsional, atau bahwa mereka percaya bahwa tidak ada bantuan yang tersedia.Gejala CMT biasanya hadir dalam dekade kedua atau ketiga kehidupan, mulai dari bayi sampai pertengahan masa dewasa, depnding pada subtipe CMT. Gejala biasanya berkembang secara bertahap dan bervariasi dalam tingkat keparahan. Beberapa mungkin memiliki gejala ringan sehingga mereka tidak melihat, sementara lainnya dengan bentuk parah dari gangguan dapat severly terganggu karena keterlibatan otot pernapasan. CMT jarang berakibat fatal, dan kebanyakan orang yang memiliki penyakit memiliki expactancy kehidupan normal.