30 yr old male, having atrophy of calf muscles in rt lower limb which gradually increased in the last 1 year, now complaining of weakness in that leg. o/e pulse:60b min, b.p. 94/64, pallor present. no other significant history present. anybdd? mean while i hav sent for ncs and mri ls spine, cbc, echo. docs please give ur valuable opinion. thank u

What is foot drop Foot drop is a gait abnormality in which the dropping of the forefoot happens due to weakness, irritation or damage to the common fibular nerve including the sciatic nerve, or paralysis of the muscles in the anterior portion of the lower leg. It is usually a symptom of a greater problem, not a disease in itself. Foot drop is characterized by inability or impaired ability to raise the toes or raise the foot from the ankle (dorsiflexion). Foot drop may be temporary or permanent, depending on the extent of muscle weakness or paralysis and it can occur in one or both feet. In walking, the raised leg is slightly bent at the knee to prevent the foot from dragging along the ground. Foot drop can be caused by nerve damage alone or by muscle or spinal cord trauma, abnormal anatomy, toxins, or disease. Toxins include organophosphate compounds which have been used as pesticides and as chemical agents in warfare. The poison can lead to further damage to the body such as a neurodegenerative disorder called organophosphorus induced delayed polyneuropathy. This disorder causes loss of function of the motor and sensory neural pathways. In this case, foot drop could be the result of paralysis due to neurological dysfunction. Diseases that can cause foot drop include trauma to the posterolateral neck of fibula, stroke, amyotrophic lateral sclerosis, muscular dystrophy, poliomyelitis, Charcot Marie Tooth disease, multiple sclerosis, cerebral palsy, hereditary spastic paraplegia, Guillain–Barré syndrome, and Friedreich's ataxia. It may also occur as a result of hip replacement surgery or knee ligament reconstruction surgery. Signs and symptom Human lower leg anatomy Foot drop is characterized by steppage gait.[1]While walking, people suffering the condition drag their toes along the ground or bend their knees to lift their foot higher than usual to avoid the dragging.[2] This serves to raise the foot high enough to prevent the toe from dragging and prevents the slapping.[3][4] To accommodate the toe drop, the patient may use a characteristic tiptoe walk on the opposite leg, raising the thigh excessively, as if walking upstairs, while letting the toe drop. Other gaits such as a wide outward leg swing (to avoid lifting the thigh excessively or to turn corners in the opposite direction of the affected limb) may also indicate foot drop.[5] Patients with painful disorders of sensation (dysesthesia) of the soles of the feet may have a similar gait but do not have foot drop. Because of the extreme pain evoked by even the slightest pressure on the feet, the patient walks as if walking barefoot on hot sand. Pathophysiology The causes of foot drop, as for all causes of neurological lesions, should be approached using a localization-focused approach before etiologies are considered. Most of the time, foot drop is the result of neurological disorder; only rarely is the muscle diseased or nonfunctional. The source for the neurological impairment can be central (spinal cord or brain) or peripheral (nerves located connecting from the spinal cord to an end-site muscle or sensory receptor). Foot drop is rarely the result of a pathology involving the muscles or bones that make up the lower leg. The anterior tibialis is the muscle that picks up the foot. Although the anterior tibialis plays a major role in dorsiflexion, it is assisted by the fibularis tertius, extensor digitorum longus and the extensor halluces longus. If the drop foot is caused by neurological disorder all of these muscles could be affected because they are all innervated by the deep fibular (peroneal) nerve, which branches from the sciatic nerve. The sciatic nerve exits the lumbar plexus with its root arising from the fifth lumbar nerve space. Occasionally, spasticity in the muscles opposite the anterior tibialis, the gastrocnemius and soleus, exists in the presence of foot drop, making the pathology much more complex than foot drop. Isolated foot drop is usually a flaccid condition. There are gradations of weakness that can be seen with foot drop, as follows: 0=complete paralysis, 1=flicker of contraction, 2=contraction with gravity eliminated alone, 3=contraction against gravity alone, 4=contraction against gravity and some resistance, and 5=contraction against powerful resistance (normal power). Foot drop is different from foot slap, which is the audible slapping of the foot to the floor with each step that occurs when the foot first hits the floor on each step, although they often are concurrent. Treated systematically, possible lesion sites causing foot drop include (going from peripheral to central): Neuromuscular disease;Peroneal nerve (common, i.e., frequent) —chemical, mechanical, disease;Sciatic nerve—direct trauma, iatrogenic;Lumbosacral plexus;L5 nerve root (common, especially in association with pain in back radiating down leg);Cauda equina syndrome, which is cause by impingement of the nerve roots within the spinal canal distal to the end of the spinal cord;Spinal cord (rarely causes isolated foot drop) —poliomyelitis, tumor;Brain (uncommon, but often overlooked) —stroke, TIA, tumor;Genetic (as in Charcot-Marie-Tooth Diseaseand hereditary neuropathy with liability to pressure palsies);Nonorganic causes. If the L5 nerve root is involved, the most common cause is a herniated disc. Other causes of foot drop are diabetes (due to generalized peripheral neuropathy), trauma, motor neuron disease (MND), adverse reaction to a drug or alcohol, and multiple sclerosis. Gait cycle Drop foot and foot drop are interchangeable terms that describe an abnormal neuromuscular disorder that affects the patient's ability to raise their foot at the ankle. Drop foot is further characterized by an inability to point the toes toward the body (dorsiflexion) or move the foot at the ankle inward or outward. Therefore, the normal gait cycle is affected by the drop foot syndrome. The normal gait cycle is as follows: Swing phase (SW): The period of time when the foot is not in contact with the ground. In those cases where the foot never leaves the ground (foot drag), it can be defined as the phase when all portions of the foot are in forward motion.Initial contact (IC): The point in the gait cycle when the foot initially makes contact with the ground; this represents the beginning of the stance phase. It is suggested that heel strike not be a term used in clinical gait analysis as in many circumstances initial contact is not made with the heel. Suggestion: Should use foot strike.Terminal contact (TC): The point in the gait cycle when the foot leaves the ground: this represents the end of the stance phase or beginning of the swing phase. Also referred to as foot off. Toe-off should not be used in situations where the toe is not the last part of the foot to leave the ground. The drop foot gait cycle requires more exaggerated phases. Drop foot SW: If the foot in motion happens to be the affected foot, there will be greater flexion at the knee to accommodate the inability to dorsiflex. This increase in knee flexion will cause a stair-climbing movement.Drop foot IC: Initial contact of the foot that is in motion will not have normal heel-toe foot strike. Instead, the foot may either slap the ground or the entire foot may be planted on the ground all at once.Drop foot TC: Terminal contact that is observed in patients that have drop foot is quite different. Since patients tend to have weakness in the affected foot, they may not have the ability to support their body weight. Often, a walker or cane will be used to assist in this aspect. Drop Foot is the inability to dorsiflex, evert, or invert the foot. So when looking at the Gait cycle, the part of the gait cycle that involves most dorsiflexion action would be Heel Contact of the foot at 10% of Gait Cycle, and the entire swing phase, or 60-100% of the Gait Cycle. This is also known as Gait Abnormalities. DiagnosisEdit Initial diagnosis often is made during routine physical examination. Such diagnosis can be confirmed by a medical professional such as a neurologist, orthopedic surgeon or neurosurgeon. A person with foot drop will have difficulty walking on his or her heels because he will be unable to lift the front of the foot (balls and toes) off the ground. Therefore, a simple test of asking the patient to dorsiflex may determine diagnosis of the problem. This is measured on a 0-5 scale that observes mobility. The lowest point, 0, will determine complete paralysis and the highest point, 5, will determine complete mobility. There are other tests that may help determine the underlying etiology for this diagnosis. Such tests may include MRI, MRN, or EMG to assess the surrounding areas of damaged nerves and the damaged nerves themselves, respectively. The nerve that communicates to the muscles that lift the foot is the peroneal nerve. This nerve innervates the anterior muscles of the leg that are used during dorsi flexion of the ankle. The muscles that are used in plantar flexion are innervated by the tibial nerve and often develop tightness in the presence of foot drop. The muscles that keep the ankle from supination (as from an ankle sprain) are also innervated by the peroneal nerve, and it is not uncommon to find weakness in this area as well. Paraesthesia in the lower leg, particularly on the top of the foot and ankle, also can accompany foot drop, although it is not in all instances. A common yoga kneeling exercise, the Varjrasana has, under the name "yoga foot drop," been linked to foot drop. Vajrasana yoga foot drop --- Yoga foot drop is a kind of drop foot, a gait abnormality. It is caused by a prolonged sitting on heels, a common yoga position of vajrasana. The name was suggested by Joseph Chusid, MD, in 1971, who reported a case of foot drop in a student who complained about increasing difficulty to walk, run, or climb stairs. The cause was thought to be injury to the common peroneal nerve, which is compressed and thereby deprived of blood flow while kneeling. Yoga foot drop is a potential adverse effect of yoga, allegedly unmentioned by yoga teachers and books

*Paralysis* *Today about* Definition Paralysis is the inability – whether temporary or permanent – to move a part of the body. In almost all cases, paralysis is due to nerve damage, not to an injury to the affected region. For instance, an injury in the middle or lower regions of the spinal cord is likely to disrupt function below the injury, including the ability to move the feet or feel sensations, even though the actual structures are as healthy as ever. The spinal cord is like the brain’s relay system, so when something in the spinal cord doesn’t work or is injured, paralysis is often the result. These injuries can be the product of traumatic accidents, or diseases such as strokes and polio. Most spinal cord injuries are incomplete, which means that some signals still travel up and down the cord. With an incomplete injury, you may retain some sensation and movement all the time, or the severity of the paralysis may change sometimes on a highly unpredictable basis. A complete spinal cord injury, by contrast, completely compressed or severs the nerves in the spinal cord, making it impossible for the signal to travel. Types of Paralysis Temporary and permanent paralysis Paralysis can either be temporary or permanent. Bell’s palsy is a relatively common cause of temporary paralysis that causes temporary facial paralysis. Sometimes paralysis that occurs after a stroke can also be temporary. Paralysis caused by serious injury, such as a broken neck, is usually permanent. Examples of localised paralysis include: Facial paralysis – which is usually limited to one side of the face Paralysis of the hand Paralysis of the vocal cords – vocal cords are bands of tissue and muscle used to generate speech; paralysis usually only affects one vocal cord, which means the person is able to speak but their voice will be hoarse There are four generalized paralysis, however, which have to do with the portion of the body that is affected. Monoplegia Monoplegia is paralysis of a single area of the body, most typically one limb. People with monoplegia typically retain control over the rest of their body, but cannot move or feel sensations in the affected limb. Cerebral palsy, injuries and ailments can lead to this form of partial paralysis, including: Strokes Tumors Nerve damage due to injuries or diseases Nerve impingement Motor neuron damage Brain injuries Impacted or severed nerves at the affected location Hemiplegia Hemiplegia affects an arm and a leg on the same side of the body, and as with monoplegia, the most common cause is cerebral palsy. Hemiplegia often begins with a sensation of pins and needles, progresses to muscle weakness, and escalates to complete paralysis. Hemiplegia should not be confused with hemiparesis, which refers to weakness on one side of the body. Nevertheless, hemiparesis is often a precursor to hemiplegia, particularly for people with neurological issues. Paraplegia Paraplegia refers to paralysis below the waist, and usually affects both legs, the hips, and other functions, such as sexuality and elimination. Though stereotypes of paraplegia hold that people with this condition cannot walk, move their legs, or feel anything below the waist, the reality of paraplegia varies from person to person and sometimes, from day to day. Spinal cord injuries are the most common cause of paraplegia. These injuries impede the brain’s ability to send and receive signals below the site of the injury. Some other causes include: Spinal cord infections Spinal cord lesions Brain tumors Brain infections Rarely, nerve damage at the hips or waist; this more typically causes some variety of monoplegia or hemiplegia. Brain or spinal cord oxygen deprivation due to choking, surgical accidents, violence, and similar causes. Stroke Congenital malformations in the brain or spinal cord Quadriplegia Quadriplegia, which is often referred to as tetraplegia, is paralysis below the neck. All four limbs, as well as the torso, are typically affected. Some quadriplegics spontaneously regain some or all functioning, while others slowly retrain their brains and bodies through dedicated physical therapy and exercise. Spinal cord injuries are the leading cause of quadriplegia. The most common causes of spinal cord injuries include automobile accidents, acts of violence, falls, and sporting injuries, especially injuries due to contact sports such as football. Traumatic brain injuries can also cause this form of paralysis. Other sources of quadriplegia include: Acquired brain injuries due to infections, stroke, and other disease-related processes. Loss of oxygen to the brain and spinal cord due to choking, anesthesia-related accidents, anaphylactic shock, and some other causes. Spinal and brain lesions Spinal and brain tumors Spinal and brain infections Catastrophic nerve damage throughout the body Congenital abnormalities Early brain injuries, especially pre-birth or during-birth injuries that lead to cerebral palsy, which can produce a range of symptoms, including varying degrees of paralysis Allergic reactions to drugs Drug or alcohol overdoses Partial or complete paralysis Paralysis can be: Partial – where there is some muscle function and sensation; for example, if a person can move one leg but not the other, or feel sensations such as cold and heat Complete – where there is complete loss of muscle function and sensation in affected limbs Spastic or flaccid paralysis Paralysis can be: Spastic – where muscles in affected limbs are unusually stiff or display spasms, and movements are not under the control of the individual (read about spastic paraplegia) Flaccid – where muscles in affected limbs are floppy and weak; muscles in flaccid paralysis may shrivel Epidemiology about paralysis in US Paralysis is dramatically more widespread than previously thought. Approximately 1.7 percent of the U.S. population, or 5,357,970 people were living with some form of paralysis, defined as a central nervous system disorder resulting in difficulty or inability to move the upper or lower extremities. The leading cause of paralysis was stroke (33.7 percent), followed by spinal cord injury (27.3 percent) and multiple sclerosis (18.6 percent). Causes The nerve damage that causes paralysis may be in the brain or spinal cord (the central nervous system) or it may be in the nerves outside the spinal cord (the peripheral nervous system). The most common causes of damage to the brain are: Stroke Tumor Trauma (caused by a fall or a blow) Multiple sclerosis (a disease that destroys the protective sheath covering nerve cells) Cerebral palsy (a condition caused by a defect or injury to the brain that occurs at or shortly after birth) Metabolic disorder (a disorder that interferes with the body’s ability to maintain itself) Damage to the spinal cord is most often caused by trauma, such as a fall or a car crash. Other conditions that may damage nerves within or immediately adjacent to the spine include: Tumor Herniated disk (also called a ruptured or slipped disk) Spondylosis (a disease that causes stiffness in the joints of the spine) Rheumatoid arthritis of the spine Neurodegenerative disease (a disease that damages nerve cells) Multiple sclerosis Damage to peripheral nerves may be caused by: Trauma Compression or entrapment (such as carpal tunnel syndrome) Guillain-Barré syndrome (a disease of the nerves that sometimes follows fever caused by a viral infection or immunization) Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) (a condition that causes pain and swelling in the protective sheath covering nerve cells) Radiation Inherited demyelinating disease (a condition that destroys the protective sheath around the nerve cell) Toxins or poisons Symptoms Usually paralysis are occur along with some of the following symptoms – Loss of consciousness (could be brief) or confusion Clumsiness and numbness Severe headache Difficulty breathing Drooling Cognitive difficulties, difficulty writing or speaking Changes in mood or behavior Loss of bladder or bowel control Loss or changes in vision and/ or hearing Nausea with or without vomiting Complications Because paralysis causes immobility, it has a rather significant effect on the other systems in the body. These include: Changes to circulation and respiration Changes to the kidneys and gastrointestinal system Changes to muscles, joints, and bones Spasticity of the limbs Muscle spasms Pressure sores Edema Blood clots in the lower limbs Feelings of numbness or pain Skin injury Bacterial infection Disruption of the normal working of the tissues, glands, and organs Constipation Loss of control of urination Sexual difficulties Abnormal sweating Abnormal breathing or heart rate Balance problems Difficulty thinking Behavioral issues Difficulty speaking or swallowing Vision problems Diagnosis The first step in diagnosis of paralysis is physical exam by the doctor. Next the doctor will talk about the symptoms and family history. Diagnosing will not be difficult if the cause of paralysis is obvious, for example, paralysis after a stroke. If the cause is not obvious, then the physician will order specialized tests such as: X-ray CT scan (Computed tomography) MRI (Magnetic Resonance Imaging) scans Electromyography (usually used to diagnose Bell’s palsy) If required the patient will then be referred to a neurologist. Treatment and Medications A wearable electronic device that helps recover arm function by delivering tiny electrical currents to the nerves thereby activating hand and arm muscles. This method is called Functional Electrical Stimulation or FES. If cure or recovery from paralysis is not possible, various mobility aids such as wheelchairs and orthoses are available for people with paralysis. Prosthetics and orthoses: Prosthesis is a device that replaces or extends a limb, extremity, or other body part. Orthoses are external mechanical devices which support, prevent, correct and assist body segments in neuromuscular skeletal conditions. Medication and aids for managing paralysis In most cases, spinal cord injury and paralysis result in the loss of normal bowel and bladder function. So, a catheter is used to empty urine from the bladder. Bowel retraining, enemas, and sometimes colostomy (surgery of the bowel) are done to help people with paralysis empty their bowel. Pain caused by nerve damage is normally relieved through medicines such as amitriptyline or pregabalin, since common painkillers like paracetamol or ibuprofen are ineffective in such type of pain. Breathing difficulties that arise through spinal cord injury to the upper neck is often treated using positive pressure ventilators that are either invasive or non-invasive. For abnormally stiff muscles (spasticity) and involuntary muscle spasms, treatment involves use of muscle relaxants such as Baclofen, Tizanidine or Dantrolene. Sometimes, Botox is given for localised spasms. A relatively new treatment for management of spastic paralysis is the intrathecalbaclofen (ITB) therapy in which consistent optimal dosage of Baclofen is delivered via a programmable drug pump implanted in the fluid-filled space around the spinal cord. It is important to note that pressure ulcers can develop if a person is unable to move regularly due to paralysis. Care must be taken to ensure that preventive measures such as changing position regularly or pressure relieving devices are used. Rehabilitation may involve: Physiotherapy – to improve mobility Speech therapy – to improve communication Occupational therapy – to improve daily functions such as eating, cooking, toileting and washing. Prevention Reducing the number of controllable risk factors is the best way to prevent a stroke. This can include: Stopping smoking Losing weight Eating a balanced diet low in sodium and saturated and trans fat Moderating alcohol intake (no more than 2 small drinks per day) Exercising regularly in order to stay physically fit Maintaining good control of existing medical conditions such as diabetes, high blood pressure and high cholesterol

A Case of muscle dystrophy last 5 year age 19 plz suggest me how can I do for patient patent is too poor no enough money for treatment....

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.