theThanks a lot dear Adnan for posting a good case for discussion. The above mentioned case seems to be a case of MUSCULAR DYSTROPHY. By definition MD is group of diseases that cause progressive weakness and loss of muscle mass. In MD abnormal genes mutations interfere with the proteins required to form a healthy muscle. Very unfortunately there is no cure for MD. But medicines and physical therapy will help manage the symptoms and slow down the course of the disease. Complications of MD. 1) Inability to walk 2) Shortening of muscles or tendons around the joints in the form of Contractures. This can further limit the mobility. 3) Breathing problems These patients may need a ventilator support initially in the night and later on during day time too. 4) Scoliosis 5) Heart problems 6) Swallowing problems. Investigations in MD. 1) No trauma, no statin and a high CK Creatinine Phosphokinase indicates muscle disease MD. 2) EMG Changes in the electrical activity confirms MD 3) Genetic testing 4) Muscle Biopsy 5) ECG 6) 2D Echo heart. 7) PFT NCS and MRI have no role in MD. Treatment There is no cure for MD. Treatment includes 1) Medical therapy 2) Physical therapy 3) Surgical and other procedures. Medical Therapy This includes 1) of Steroids 2) Heart drugs like ACEI Beta blockers Physical therapy 1) Range of motion and stretching exercises 2) Low impact aerobic exercise like Walking Swimming 3) Braces 4) Mobility Aids 5) Breathing exercises. Surgery Surgery for Scoliosis may further worsen breathing. Prognosis is very poor. Better counsel the patient and family members about the pros and cons to avoid further complications.
Muscular dystrophy is always bilateral except in very few case report of osteo arthritis of ankle and knee joint. There are various Muscular dystrophy identified like Duchene's which is the most common variant, hereditary inclusion body myositis (myopathy) type 1 (HIBM1), Gowers-Laing distal myopathy, Finnish (tibial) distal myopathy etc. The above case is most like of Focal muscular atrophy (FMA). Muscle wasting is probably the presenting symptom and the onset is insidious. The organ ultimately affected is the muscle, although the pathology may be anywhere along the lower motor neuron (LMN) or, at times, secondary to non neurological disorders. Etiologic factors include the following: Infection, Trauma, Inflammation, Spinal cord disorders, Vasculitis, Nerve Entrapment, physical agents, such as electrical or radiation injury, Genetic and enzyme defects. etc. EMG & MRI- spine will be useful to know the level of nerve injury.
About MND 1) Per se MND motor neuron disease is Bilateral. 2) MND is a very rare disease like the incidence is 2 cases out of 1,00,000 population. 3) Progressive muscular atrophy is a v uncommon form of MND. 4) The muscles affected first are the small muscles of hand and foot. 5) Muscle spasticity is absent in MND. 6) Primary Lateral Sclerosis is a rare variant of MND which may cause weakness in the leg muscles.
There is significant wasting of the right leg,straight forward case of wasted leg syndrome where in such cases will have assymetrical slow,non progressive lmn type of weakness which involves the posterior crural -calf muscles followed by anterior crural and quadriceps.
Contd. 7) There is no diagnostic test for MND. 8) There is no specific treatment for MND 9) The prognosis is very poor for MND.
thank u all for such good replies. pateint will come with reports on monday so as soon as he comes ill surely share it.
Any sensory symptoms /finding? If no with unilateral atrophy consider motor neuron disease. Rule out dm, Hansen.
SMA or a wasted leg syndrome-variants of mnd,SMA has a better prognosis.EMG to confirm the diagnosis .
Dear Adnan, Can you please share your reports ???
I agree with Dr. Krsna Mohan sir
Cases that would interest you
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12 yr old boy with progressive weakness in all four limb and dysarthia.Dr. Ramesh Kumbhkar2 Likes16 Answers
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An 16 years old male is having weakness of left upper limb with wasting over a period of last 6 months. Also gives history weaked grip of left hand . Apparently everything looks normal as no other symptoms What next should be done for further evaluation of this caseDr. Parveen Yograj17 Likes22 Answers
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Mumps Mumps is an infection caused by a type of virus called a paramyxovirus. It is very contagious and spread in saliva, the same way as a cold or flu. This means it can be caught from an infected person coughing, sneezing, etc. It can also be caught from touching infected objects – for example, door handles. ￼ ￼ Mumps virions are pleomorphic particles ranging from 100 to 600 nm in size, consisting of a helical ribonucleoprotein (RNP) core surrounded by a host cell–derived lipid envelope. The RNP consists of a single-stranded RNA (ssRNA) molecule coated by the viral nucleoprotein. The RNP appears to be a hollow tube with a unit length of approximately 1 mm, a diameter of 17 to 20 nm, and a central core of 5 to 6 nm. The viral host cell–derived envelope contains the viral glycoproteins that project 12 to 15 nm from the virion surface. ￼ Spreading and incubation period of Paramyxovirus The virus is acquired by respiratory droplets. It replicates in the nasopharynx and regional lymph nodes.After 12 to 25 days a viremia occurs, which lasts from 3 to 5 days. During the viremia, the virus spreads to multiple tissues, including the meninges, and glands such as the salivary, pancreas, testes, and ovaries.Inflammation in infected tissues leads to characteristic symptoms of parotitis and aseptic meningitis.The incubation period of mumps is 14 to 18 days (range, 14 to 25 days). History In the 5th century bc, Hippocrates described a mild epidemic illness associated with nonsuppurative swelling near the ears and, variably, with painful swelling of one or both testes. These descriptions of parotitis and orchitis, respectively, are the hallmarks of mumps virus (MuV) infection. The name mumps may derive from an old English verb that means to grimace, grin, or mumble. Hamilton, a physician of the late 18th century, is credited as being the first to associate central nervous system (CNS) involvement with mumps in his description of the neuropathology of a fatal case. Later studies would reveal MuV as a highly neurotropic agent and a leading cause of virus-induced aseptic meningitis and encephalitis. A number of laboratory investigations suggested that a filterable, transmissible agent was responsible for mumps. However, a viral etiology was not proven until 1935 when Johnson and Goodpasture, using bacteria-free parotid secretions, successfully transmitted the disease between monkeys and children and then back to naïve monkeys, fulfilling Koch’s postulates. The demonstration by Habel145 and Enders108 in 1945 that MuV could be isolated and propagated in embryonated eggs enabled the demonstration of the hemagglutinating, hemolytic, and neuraminidase properties of the virus, leading to the development of an inactivated vaccine in 1946 and to the first live virus vaccine in 1958. The introduction of tissue culture as a practical alternative for the propagation and study of the virus in 1948 was pivotal for advancing studies of the epidemiology and pathogenesis of the disease as well as the molecular biology of the virus, permitting the development of cell-based vaccines. Epidemiology at worldwide The mumps virus is present throughout the world and hence, risk of exposure to mumps outside the United States may be high. In many countries worldwide, mumps remains endemic. The mumps vaccine is in use in only 57% of countries belonging to the World Health Organization (WHO), predominantly those countries with more developed economies. Worldwide variations in the number of persons who receive the mumps vaccination make it difficult to estimate the number of cases. The incidence varies markedly from region to region. Causes of mumps Mumps is due to an infection by the mumps virus. It can be transmitted by respiratory secretions (e.g. saliva) from a person already affected with the condition. When contracting mumps, the virus travels from the respiratory tract to the salivary glands and reproduces, causing the glands to swell. Examples of how mumps can be spread include: Sneezing or coughing.Using the same cutlery and plates as an infected person.Sharing food and drink with someone who is infected.An infected person touching their nose or mouth and then passing it onto a surface that someone else may touch. Individuals infected with the mumps virus are contagious for approximately 15 days (6 days before the symptoms start to show, and up to 9 days after they start). What are risk factors for contracting mumps? Failure to vaccinate completely (two separate doses) with exposure to those with mumpsAge: The highest risk of contracting mumps is to a child between 2-12 years of age.Season: Outbreaks of mumps were most likely during the winter/spring seasons.Travel to high-risk regions of the world: Africa, general Indian subcontinent region, and Southeast Asia. These areas have a very low rate of immunization.Weakening immune system: either due to diseases (for example, HIV/AIDS, cancer) or medication (oral steroid use for more than two weeks, chemotherapy).Born before 1956: Generally, these individuals are believed to have experienced mumps infection in childhood. However, if they did not, they are at risk for adult mumps disease. Signs & Symptoms of Mumps The most common symptoms include: FeverHeadacheMuscle achesTirednessLoss of appetiteSwollen and tender salivary glands under the ears on one or both sides (parotitis) Symptoms typically appear 16-18 days after infection, but this period can range from 12-25 days after infection. Some people who get mumps have very mild or no symptoms, and often they do not know they have the disease. Most people with mumps recover completely in a few weeks. Notify your healthcare provider if you have any of the following: Swelling that lasts longer than seven daysHeadaches not relieved with medicationOngoing feverNausea and vomitingSwelling accompanied by redness or warmthDecreased hearingNeck stiffnessPain or swelling in testicles (male)Abdominal Pain Complications of mumps Complications are more frequent in adults than children, the most common are: Orchitis – testicles swell and become painful, this happens to 1 in 5 adult males with mumps. The swelling normally goes down within 1 week; tenderness can last longer than that. This rarely results in infertility.Oophoritis – ovaries swell and are painful; it occurs in 1 in 20 adult females. The swelling will subside as the immune system fights off the virus. This rarely results in infertility.Viral meningitis – this is one of the rarest of the common complications. It happens when the virus spreads through the bloodstream and infects the body’s central nervous system (brain and spinal cord).Inflamed pancreas (pancreatitis) – pain will be experienced in the upper abdomen; this occurs in 1 out of 20 cases and is usually mild.Electrocardiogram changes compatible with myocarditis are seen in 3%–15% of patients with mumps, but symptomatic involvement is rare. Complete recovery is the rule, but deaths have been reported. If a pregnant woman contracts mumps in the first 12-16 weeks of her pregnancy, she will have a slightly increased risk of miscarriage. Rarer complications of mumps include: Encephalitis – the brain swells causing neurological issues. In some cases, this can be fatal. This is a very rare risk factor and affects just 1 in 6,000 cases.Hearing loss – this is the rarest of all the complications affecting just 1 in 15,000.Other less common complications of mumps include arthralgia, arthritis, and nephritis. Tests and diagnosis of mumps Normally, mumps can be diagnosed by its symptoms alone, especially by examining the facial swelling. A doctor might also: Check inside the mouth to see the position of the tonsils – when infected with mumps, a person’s tonsils can get pushed to the side. Take the patient’s temperature.Take a sample of blood, urine, or saliva to confirm diagnosis.Take a sample of CSF (cerebrospinal fluid) from the spine for testing – this is usually only in severe cases. Treatment Because mumps is viral, antibiotics cannot be used to treat it, and at present, there are no anti-viral medications that can treat mumps. Current treatment can only help relieve the symptoms until the infection has run its course and the body has built up an immunity, much like a cold. In most cases, people recover from mumps within 2 weeks. Due to the viral nature of mumps, treatment focuses on decreasing symptoms. Eat soft, bland foods that do not require much chewing. Examples include oatmeal, bananas, pasta, potatoes, eggs, gelatin, cooked vegetables, applesauce and tender cooked meats.Avoid tart drinks and sour foods since they can irritate the swelling and cause pain. Examples of these include orange juice, salad dressing, and pickles.Apply heat or cold packs to the cheeks. Some people find warm compresses to be more soothing while others from cold compresses provide more pain relief.Use over-the-counter medication such as acetaminophen or ibuprofen to reduce fever and pain.Get extra rest and stay well hydrated with plenty of fluids such as water, Sprite, bouillon, milk and popsicles.If orchitis develops, treat this with bed rest, ice packs, ibuprofen and provide support to inflamed testicles by wearing tight fitting underwear or an athletic supporter. Prevention Immunisation given on-time is the best method of preventing mumps. The measles, mumps, rubella vaccine (MMR) is given as part of the immunisation schedule at 15 months and 4 years of age. No mumps-only vaccine is available in New Zealand.People with mumps are excluded from early childhood education, school and work until nine days after the appearance of swollen salivary glands to protect others from infection.Contacts of mumps cases, who are not immune to mumps e.g. those who are unvaccinated, are excluded from early childhood education, school and work until 25 days after the appearance of swollen glands in the last case they were in contact with.Anyone born after the 1990s would most probably have been given the MMR vaccine but, if unsure, it is always good to check with a doctor. MMR vaccine side effects Most people given the MMR vaccine do not suffer side effects, and the disease itself cannot be contracted from the vaccine. A small percentage might develop a rash or fever and possibly aches in their joints. Preventing the spread of mumps There are a number of precautions that help prevent the spread of infection; these are: Washing hands with water and soap frequently. ￼ Not going into work/school until 5 days after the symptoms start.Covering the nose and mouth with a tissue when sneezing or coughing.Dr. Shailendra Kawtikwar5 Likes14 Answers
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MND.. Motor Neuron Diseases(MNDs) are a Progressive Neurodegeneration that destroy Motor Neurons.. There are 2 types of Motor Neurons 1) Upper Motor Neurons 2) Lower Motor Neurons and other lowes motor neurons just attached to immediate bodies. The cells that control essential voluntary muscle activity namely speaking,walking,breathing,swalling. Generally messages from nerve cells in the Brain( called Upper Motor Neurons) are transmitted to nerve cells in the Brain Stem and Spinal Cord ( lower motor neurons) and from them to particular muscles. Upper Motor Neurons direct the Lower Motor Neurons and Lower Motor Neurons control movement in the arms,legs etc. When there are disruptions in the Spinals between the Lowest Motor Neurons and the muscles gradually weaken and may begin wasting away and developed uncontrolleble twitching called Fascination. And when disruptions of signals between Upper Motor Neurons and Lower Motor Neurons then rigidity takes place that is called Spasticity.. knee jerk and ankle jerk overactive and voluntary movement can be lost. treatment.... 1) Medorrhenum 200 one dose at seven days interval.. 2) Gelsemium 200 one dose in every morning.. 3) Physiotherapy.. Thank you.. Dr Anutosh Chakraborty.Dr. Anutosh Chakraborty10 Likes13 Answers
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Neuro-otological syndromes for the neurologist :-- ---------------------------------------------------------------- Neurologists may be tempted to regard deafness as “somebody else’s problem”—generally the cause will lie within the remit of an ear, nose, and throat (ENT) specialist. While such an approach is often reasonable, there are a number of circumstances in which knowledge of deafness and the syndromes with which it can be associated can take on real importance. Neurologists need to structure their thinking about loss of hearing and be aware of the neurological syndromes that may present with deafness as a component. The complaint can thus be used as “part of the puzzle” when constructing a differential diagnosis in the neurology clinic, and acknowledged and referred to an ENT colleague when the problem is non-neurological. CAUSES OF HEARING LOSS Hearing is the result of complex processes involving the structure of the ear, the function of the inner ear and vestibulum, and the function of the auditory nerve. Peripheral hearing loss can be divided into two main categories, which may co-exist in the same patient. Conductive hearing loss is caused by failure of sound conduction from the environment to the inner ear, and is usually due to problems in the external ear, eardrum, tympanic membrane or middle ear. Common causes include malformations, middle ear infections, trauma causing disruption of the eardrum or middle ear, and stiffness of the eardrum or middle ear bones (otosclerosis). Sensorineural hearing loss (SNHL) is the result of disorders of the inner sensory apparatus. It can be caused by problems in the inner ear, cochlea, auditory nerve, or auditory nerve nucleus. Although some “neurological” diseases are associated with conductive hearing loss, generally neurological causes are sensorineural. Peripheral neurological causes of SNHL are listed in table 1. The text and tables that follow expand on the categories in table 1, highlighting particularly the syndromic diseases and patterns that can include hearing loss. Central hearing loss (or disorders of central auditory processing) are dealt with in the second section of this article. Table 1 Peripheral neurological sensorineural hearing loss GENETIC Syndromic A number of different causes of genetically inherited deafness are syndromically recognisable.1 Most present in children, and examples are given below: Alport syndrome—renal failure, SNHL, and retinopathy presenting in the first decade. Treacher-Collins syndrome—An autosomal dominant disorder of craniofacial development, causing external ear abnormalities, atresia of external auditory canals and malformation of ossicles (and therefore conductive deafness), downward sloping palpebral fissures, eyelid colobomas, mandible hypoplasia and cleft palate. Pendred syndrome—An autosomal recessive disorder consisting of SNHL and diffuse thyroid enlargement. Causes about 5% of childhood deafness Usher syndrome—A congenital disease causing sensorineural deafness and vestibular disorder. Progressive retinitis pigmentosa and ataxia begin in late childhood or adolescence. Sometimes patients have learning difficulties, cataracts and glaucoma. Waardenburg’s syndrome—An auditory–pigmentary syndrome causing congenital SNHL which is observed at all ages. Absence of melanocytes from the skin, hair, and eyes causes pigmentary abnormalities. Dystopia canthorum (lateral displacement of the inner canthus of each eye) and arm abnormalities may be seen. The major genetic syndromic cause of deafness likely to present to adult neurologists is neurofibromatosis type 2. Neurofibromatosis type 2 (NF2) Neurofibromatosis type 2 (NF2) is an autosomal dominant disorder caused by inactivating mutations of the NF2 gene. It is much less common than neurofibromatosis type 1, accounting for 5–10% of neurofibromatosis cases. Historically the two conditions have been grouped together (“von Recklinghausen disease” or “multiple neurofibromatosis”), chiefly because café-au-lait spots and peripheral nerve tumours can occur in either. In the 1980s the greater morbidity and mortality in NF2, the mapping of the NF2 gene to chromososme 22, and the appreciation that acoustic neuromas are absent in NF1, culminated in the consensus opinion that the two conditions were distinct. Approximately half of diagnosed patients have no family history and are presumed to represent new mutations. Clinically NF2 comprises the development of nervous system tumours, ocular abnormalities, and skin tumours. Various diagnostic criteria have emerged, with the “Manchester” criteria2 being shown to be the most sensitive. MANCHESTER CLINICAL DIAGNOSTIC CRITERIA FOR NF2 Note: “any two” means two individual tumours or cataracts. Bilateral vestibular schwannomas First degree family relative with NF2 and unilateral vestibular schwannoma or any two of the following: meningioma, schwannoma, glioma, neurofibroma, posterior subcapsular lenticular opacities Unilateral vestibular schwannoma and any two of the following: meningioma, schwannoma, glioma, neurofibroma, posterior subcapsular lenticular opacities Multiple meningiomas (two or more) and unilateral vestibular schwannoma or any two of the following: schwannoma, glioma, neurofibroma, cataract. Vestibular schwannomas (usually, but not always, bilateral) occur in ∼95% of adult patients with NF2 (fig 1A,B). Mean age at onset is 22 years, and it is rare to present after the age of 50 years. Presentation is usually with tinnitus, alteration in hearing or vestibular symptoms attributable to vestibular schwannoma, but in the 18% of patients that present in childhood, initial symptoms of a meningioma, spinal or cutaneous tumour are more common. The best predictor of mortality is age at diagnosis. Other important predictors are the presence of intracranial meningiomas, the type of constitutional NF2 mutation, and the type of treatment centre.3 In general people with constitutional nonsense or frameshift mutations have severe disease, those with missense mutations, in-frame deletions, or large deletions have mild disease, and those with splice site mutations have variable disease severity.4 Multiple NF2 patients in the same family often have similar disease severity, but specific disease features and disease progression can differ even between monozygotic twins with NF2. In families with early onset neurofibromatosis 2, screening should probably begin in childhood, and if magnetic resonance imaging (MRI) shows no evidence of schwannoma at 30 years, the likelihood of gene inheritance is considered remote. Vestibular schwannoma growth rates are extremely variable. Opinions about management once they are detected remain controversial and are still evolving. Some NF2 patients with unilateral vestibular schwannomas, and a subgroup with bilateral tumours that progress slowly, may be asymptomatic or have mild or stable symptoms for a long time. Such patients, if MRI shows no change in the size of the tumour, can be clinically and radiologically observed. However, vestibular schwannomas in NF2 are generally more invasive than isolated schwannomas (fig 1C,D). Both microsurgery and radiation treatment have a role in management. Patients with NF2 should be referred to specialty treatment centres to be managed by a multidisciplinary team expert in their disorder.3,4 The large majority of patients with NF2 develop substantial or total deafness. Some develop blindness from progression of the subcapsular lens opacities to cataracts, or morbidity from other tumours. Mortality from NF2 is high, the mean age at death being around 40 years, with a mean survival after diagnosis of 15 years.2 Death usually occurs from progressive growth of vestibular schwannomas causing increased intracranial pressure from brainstem displacement. Non-syndromic The most common forms of genetic deafness are non-syndromic.5 Inheritance is usually in an autosomal recessive pattern. Both X linked and dominant forms occur, but autosomal recessive inheritance accounts for more than 75% of childhood pre-lingual deafness. The most recent data on genetic loci can be obtained at the Hearing Loss Homepage (www.uia.ac.be/dnalab/hhh/). MITOCHONDRIAL Mitochondria derive from the ovum and, as a general rule, mitochondrial mutations are passed via the female pedigree. Pathogenic mutations affect a proportion of the mitochondrial genome, and mutant and wild type mitochondria coexist in the same cell, a situation known as heteroplasmy. A minimum number of mutant mitochondria must be present before a tissue exhibits signs of dysfunction, and the threshold for disease is lower in cell types dependent on high degrees of oxidative phosphorylation, such as brain, skeletal muscle, heart and endocrine organs. Heteroplasmy and the threshold effect partly explain the degree of phenotypic heterogeneity seen in this group of conditions, and the relatively poor correlation between genotype and phenotype. MITOCHONDRIAL SYNDROMIC Syndromic hearing impairment secondary to mitochondrial mutations occurs most commonly in MELAS (mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes), MERRF (myoclonic epilepsy with ragged red fibres) and Kearns-Sayre syndrome (KSS). The clinical features of these disorders are summarised in table 2. The mitochondrial mutation found in MELAS (3243A to G) is also found in maternally inherited diabetes and deafness (MIDD), in which progressive SNHL is associated with young onset diabetes mellitus. Table 2 Clinical features of mitochondrial syndromes associated with deafness MITOCHONDRIAL NON-SYNDROMIC It is uncertain why the mitochondrial mutations resulting in non-syndromic hearing loss preferentially affect hearing. Five such mutations have been described: 1555A to G, 7445A to G, 7472insC, 7510T to C, and 7511T to C.6 Carriers of the 1555A to G mutation are susceptible to hearing impairment after aminoglycoside antibiotics, even at normal therapeutic levels. The 7472insC mutation results in a phenotypic spectrum ranging from progressive SNHL as the sole manifestation to a severe neurological syndrome associated with ataxia, dysarthria, or rarely myoclonus. Affected members of the same pedigree may have different levels of phenotypic expression, emphasising the importance of an accurate family history. DIAGNOSING MITOCHONDRIAL DISEASE Diagnosis of mitochondrial disease may be a straightforward process of pattern recognition and appropriate investigation. However, heteroplasmy and the threshold effect result in great variation in phenotype within the tissues of individual patients, and within different individuals of the same family. Most mitochondrial syndromes present before the age of 40 years. A detailed general medical history may reveal the presence of diabetes, hypoparathyroidism, cardiomyopathy, cardiac conduction block, or pancreatic dysfunction. Family history is crucial, concentrating on the maternal pedigree, remembering that carriers may be oligo- or asymptomatic. Diseases secondary to mitochondrial deletions (for example, KSS) usually occur sporadically, and so a negative family history does not exclude the possibility of mitochondrial disease. Examination should note the presence of short stature and any evidence of psychomotor retardation, visual loss (cortical blindness, optic atrophy, retinitis pigmentosa), ptosis, ophthalmoplegia, SNHL, myopathy, neuropathy, or movement disorders such as myoclonus or dystonia. Blood tests should include a blood count, electrolytes (renal tubular acidosis may occur in KSS and MELAS) and creatine kinase (which may be elevated). Serum lactate and pyruvate are often elevated at rest and increase further on modest exercise. Cerebrospinal fluid (CSF) examination may reveal elevated protein in KSS and MERRF, although this rarely exceeds 1 g/l. An ECG may show the pre-excitation of Wolff-Parkinson-White syndrome in MERRF and cardiac conduction block in KSS. An electroencephalogram (EEG) may demonstrate epileptiform discharges in MERRF and MELAS. MRI of the brain may demonstrate high signal lesions on T2 weighted scans in MELAS, especially posteriorly and characteristically not corresponding to the territory of a single major vessel. Calcification of the basal ganglia may be seen in all mitochondrial syndromes. KSS may be associated with a leucoencephalopathy, whereas atrophy is a more common finding in MERRF. Nerve conduction studies and electromyography (EMG) may demonstrate myopathy and/or a neuropathy, which is usually axonal. Muscle biopsy may demonstrate ragged red fibres when stained with modified Gomori trichrome. Staining with cytochrome c oxidase (COX) is negative in MERRF and KSS, but most ragged red fibres stain positively in MELAS. A further characteristic feature of MELAS on muscle biopsy is the overabundance of mitochondria in smooth muscle and endothelial cells of intramuscular blood vessels. Molecular genetic testing is available for common mitochondrial mutations. In the case of MERRF and MELAS, the mutation can be detected from blood leucocytes. Heteroplasmy results in varying tissue distribution of mutated mitochondrial DNA, and so in patients presenting with only a few symptoms of MERRF or MELAS, the mutation may be undetectable in leucocytes, and may only be detected in other tissues such as cultured skin fibroblasts, oral mucosa, or (most reliably) skeletal muscle. The deletion associated with KSS is only observed in muscle mitochondria, and therefore cannot be detected in lymphocytes or fibroblasts. DISORDERS WITH INDIRECT MITOCHONDRIAL INVOLVEMENT Other disorders causing deafness may be associated indirectly with mitochondrial dysfunction, although the precise mechanism remains controversial. Cytosolic proteins are imported into mitochondria by means of mitochondrial tagging signals. One mutation of the mitochondrial protein importation mechanism has been described which results in Mohr-Tranebjaerg syndrome, an X linked recessive disorder causing progressive SNHL, dystonia, and psychiatric symptoms.7 Friedreich’s ataxia, in which deafness is an occasional feature, is caused by an expansion of GAA trinucleotide repeats in the FRDA gene encoding frataxin. Frataxin is targeted to mitochondria and has a role in iron homeostasis. Mitochondrial dysfunction may be a final common pathogenic mechanism in these conditions. AUTOIMMUNE Immune mediated inner ear disease (IMIED) is a well recognised presentation of systemic autoimmune disease, but has an uncertain pathogenesis. Animal experiments have refuted the traditional concept of the inner ear being an “immunologically privileged” site, and in 1979 a series of patients with bilateral progressive SNHL responsive to steroids was described.8 However, evidence for specific autoimmunity is indirect, being chiefly derived from clinical observations of SNHL in systemic autoimmune disease, and steroid responsiveness in patients with otherwise unexplained hearing loss.9 Autoimmunity has since been proposed as an aetiologic factor in other disorders originally thought to have an alternative pathogenesis—for example, Ménière’s disease (see Luxon, p iv45). IMIED characteristically presents subacutely over weeks to months, though can be either insidious (over years) or sudden. It tends to be progressive, but may fluctuate, and hearing loss tends to involve high frequencies. It is bilateral in most cases, though generally asymmetric and asynchronous, weeks or months separating involvement of the two sides. Other vestibulo-auditory symptoms are common including aural fullness, tinnitus, lightheadedness, and vertigo, and this can lead to confusion with Ménière’s disease. Underlying systemic autoimmune disease is common, but hearing loss may be its presenting feature. Like other autoimmune disorders, prevalence is highest in middle aged females. Table 3 lists the common systemic autoimmune diseases with which IMIED is associated, and provides diagnostic pointers for each.10 An audiogram is useful to detect high frequency hearing loss that may be asymmetric as well as being useful in monitoring treatment response; exclusion of syphilis is important since it can present in a similar fashion. Routine laboratory tests are often normal—serum testing for antibodies to a non-organ specific 68-kD antigen has proved the most specific diagnostic test, but is not readily available, and the relation of these antibodies to disease pathogenesis and course requires further definition. Table 3 Autoimmune syndromes associated with hearing loss IMIED is an important diagnosis to consider because it is reversible. While clinical history and context remain the cornerstones of diagnosis, the other essential feature that separates IMIED from other causes of SNHL is steroid responsiveness—the hearing loss should improve with treatment, and deteriorate on discontinuation of treatment. Steroids are managed in the same way as other autoimmune conditions, and plasmapheresis can be used as an alternative or an adjunct. Many experts add cyclophosphamide or methotrexate if patients deteriorate or demonstrate a partial response.10 Azathioprine may be useful as a steroid sparing agent. The anticipated outcome without treatment is sensorineural deafness, but patients who are non-responders should not be subjected to increasingly aggressive immunosuppression. Those who respond to treatment have a course often characterised by fluctuation, with relapses occurring on steroid reduction, and many may require long term immunosuppression. Prognosis for hearing is good in responders. Metabolic There are several inherited disorders of metabolism associated with deafness, many of which have additional neurological features. These conditions are described in an extensive review by Konigsmark,11 and only a few illustrative examples will be discussed further here. Refsum’s disease Refsum’s disease is an autosomal recessive disorder characterised by defective peroxismal α oxidation of phytanic acid. As a result, patients are unable to metabolise phytanic acid, resulting in an accumulation in tissues. Symptoms begin in late childhood, adolescence, or early adult life. Hearing loss is a common association, although the cardinal clinical features are retinitis pigmentosa, cerebellar signs, and chronic polyneuropathy. The sensorimotor neuropathy is distal and symmetric, and affects the lower limbs more than the arms. Reflexes are lost and all sensory modalities are affected. Nerves may or may not be palpably enlarged. Neurophysiology shows slowed motor nerve conduction velocities. Cardiomyopathy and ichthyosis (especially on the shins) are common. Anosmia and night blindness may precede the cardinal clinical features by many years. Investigations demonstrate a raised CSF protein, and all patients have greatly elevated serum concentrations of phytanic acid. Phytanic acid α oxidase activity can be measured in cultured fibroblasts. Untreated, the disease is steadily progressive, although there may be periods of apparent deterioration or remission. The importance of considering the diagnosis of Refsum’s disease is that when dietary phytanic acid is reduced, the progression of the disease is arrested and indeed some clinical improvement may occur. Plasmapheresis at the time of diagnosis may also be useful to accelerate clinical improvement. Mucopolysaccharidoses Deafness may also be a prominent feature of the mucopolysaccharidoses, disorders in which lysosomal enzyme deficiencies result in the tissue accumulation and increased urinary excretion of mucopolysaccharides. These conditions present in childhood and six syndromes are recognised, of varying severity. Clinical features typically include coarse facies, corneal clouding, organomegaly, bone and joint abnormalities, short stature, and in some cases psychomotor retardation. The diagnosis is suggested by the findings of vacuolated lymphocytes on blood film and the accumulation of glycosaminoglycans in the urine. There is some clinical overlap with the mucolipidoses, lysosomal storage disorders, and glycoprotein storage diseases (for example, mannosidosis). Definitive diagnosis rests on specific enzyme assays in leucocytes or cultured skin fibroblasts. Miscellaneous Neurosarcoidosis In the largest series to date, 72% of patients with neurosarcoidosis presented with cranial nerve palsies, optic nerve palsies forming the majority.12 However, eighth nerve palsy causing auditory or vestibular impairment occurred in 6% of cases, and deafness occurred in 7% of cases in one of the earliest series.13 Granulomatous vasculitis may lead to ischaemia or granulomatous infiltration may cause nerve compression. Clues include cervical adenopathy, skin lesions, parotid swelling, and abnormal chest x ray. Susac syndrome This is a rare syndrome comprising the clinical triad of encephalopathy, retinopathy, and hearing loss, largely in women. SNHL is often the presenting feature, but may be subclinical, only becoming evident on an audiogram. It may be unilateral or bilateral, and often presents in conjunction with vestibular symptoms or tinnitus. The retinopathy consists of multiple retinal branch occlusions, and the encephalopathy has both cognitive (memory disturbance) and psychiatric components. Pathology of involved structures points to a non-inflammatory vasculopathy. Anti-inflammatory and antiplatelet strategies are sometimes employed, but the disease often fluctuates initially then becomes self limiting. Superficial siderosis Superficial siderosis is a rare disorder that causes SNHL in association with slowly progressive cerebellar ataxia. Pyramidal signs may also be present, and dementia and bladder disturbance occur in some cases. There has been controversy regarding the aetiology of superficial siderosis, since it was initially hypothesised to be secondary to a metabolic disease analogous to haemochromatosis, but it is now accepted that it is caused by chronic subarachnoid haemorrhage. The diagnosis is often not suspected clinically, but the appearances on T2 weighted MRI are striking, showing a black rim (haemosiderin) around posterior fossa structures and cerebral sulci (fig 2). Disorders of central auditory processing There are inherent difficulties in the diagnosis and classification of the central auditory processing disorders: separating a specific difficulty with “complex sound processing” from a peripheral hearing or language disorder, which will often co-exist in the same patient, is fraught with uncertainty. These disorders cause problems with detecting the pattern in sound in one or more of four dimensions (frequency, time, amplitude, and space), at a lower cognitive level than a language disorder, but at a higher level than peripheral hearing loss.14 Many developmental presentations have been described in children and will not be considered here. In adults, specific syndromes are recognised, but are often masked by variability in clinical presentation. The common causes are stroke, head injury, and brain tumours. Comprehension, reading, and writing are preserved in “pure” syndromes, in which there is no co-existent aphasia. Cortical deafness This can be defined as the loss of the perception of sound caused by cortical damage. The patient normally presents with deafness. The contribution of attentional deficits is often difficult to assess, and inconsistency in response to sounds is a common feature. Usually there are abnormalities on audiometry, but patients have normal brainstem auditory evoked potentials. Cortical deafness is caused by bilateral lesions affecting the superior temporal gyrus: most reported cases have involved damage to the primary auditory area in Heschl’s gyrus bilaterally. The most common pathology is bilateral temporal lobe stroke, normally occurring in a stepwise fashion. Auditory agnosias An agnosia is a failure to recognise an environmental stimulus, despite intact sensory function. Patients with auditory agnosias have disordered perception of certain sounds (those with a complex structure) in the presence of preserved hearing. Such sounds include speech (“pure word deafness”), music (“amusia”) and environmental sounds (“environmental sound agnosia”). There is often pronounced overlap between the specific auditory agnosia syndromes—patients with word deafness generally exhibit some non-verbal auditory agnosia as well—supporting the hypothesis that the problem lies in being able to appreciate the pattern of sound in time and space at an intermediate level. Auditory perception is commonly tested with batteries of words, environmental stimuli and music, and most studies make no attempt to categorise the perception of simple patterned sounds, thus making clear distinction from higher cognitive disorders difficult. The picture may be further complicated by a degree of peripheral or cortical deafness, but there are several reported cases in which audiometry was normal.14 Brain stem auditory evoked potentials are normal. Again, pathology is usually vascular, and usually bilateral, with the superior temporal lobes being the site of damage. The left hemisphere appears to have greater participation in processing speech, and the right hemisphere has greater participation in processing non-speech acoustic signals. This observation has been supported recently by functional MRI data, which suggest that the right anterior superior temporal gyrus may respond more strongly to non-speech verbal sounds, while the same area on the left is more specific to speech sounds.15 Cortical auditory disorders tend to persist, and treatment is directed at the specific deficit in auditory perception. Patient and carer education is a key factor.Dr. Ved Srivastava1 Like3 Answers