Function of the Spinal cord

The spinal cord includes sensory reception from the peripheral nervous system. It also conducts motor information which consist of the body's skeletal muscles, cardiac muscles, smooth muscles, and glands. There are 31 pairs of spinal nerves along the spinal cord. These nerves each contain both sensory and motor axons. The spinal cord is protected by vertebrae, and connects the peripheral nervous system to the brain, and it acts as a ‘minor’ coordinating center.

There are four main causes of infections of the central nervous system (CNS): bacterial, viral, fungal and protozoal.

List of Viral infections

• Viral meningitis
• Eastern equine encephalitis
• St Louis encephalitis
• Japanese encephalitis
• West nile encephalitis
• Herpes simplex encephalitis
• Rabies
• California encephalitis virus
• Varicella-zoster encephalitis
• La crosse encephalitis
• Measles encephalitis
• poliomyelitis

slow virus infections, which include:

• Subacute sclerosing panencephalitis
• Progressive multifocal leukoencephalopathy
• Acquired immune deficiency syndrome (AIDS)

Simple explanation

NF-1 is a tumor disorder that is caused by the malfunction of a gene on chromosome 17, that is responsible for control of cell division. NF1 causes non cancerous lumps. NF2 often comes with scoliosis (curvature of the spine), cafe au lait spots, learning difficulties, eye problems and epilepsy.

Clinical findings

Peripheral nervous system lesions

A neurofibroma is a mass lesion of the peripheral nervous system. Its cellular lineage is uncertain, and may derive from Schwann cells, other perineural cell lines, or fibroblasts. Neurofibromas may arise sporadically, or in association with NF-1. A neurofibroma may arise at any point along a peripheral nerve. A cutaneous neurofibroma manifests as single or multiple firm, rubbery bumps of varying sizes on a person's skin. A solitary neurofibroma may also occur in a deeper nerve trunk, and only be seen on cross-sectional imaging (e.g., computed tomography or magnetic resonance) as a fusiform enlargement of a nerve.

The hallmark lesion of NF-1 is the plexiform neurofibroma. These lesions are composed of sheets of neurofibromatous tissue that may infiltrate and encase major nerves, blood vessels, and other vital structures. These lesions are difficult and sometimes impossible to routinely resect without causing any significant damage to surrounding nerves and tissue.

When a plexiform neurofibroma manifests on a leg or arm, it will cause extra blood circulation, and may thus accelerate the growth of the limb. This may cause considerable difference in length between left and right limbs. To equalize the difference during childhood, there is an orthopedic surgery called epiphysiodesis, where growth at the epiphyseal (growth) plate is halted. It can be performed on one side of the bone to help correct an angular deformity, or on both sides to stop growth of that bone completely. The surgery must also be carefully planned with regard to timing, as it is non-reversible. The goal is that the limbs are at near-equal length at end of growth.

Schwannomas are peripheral nerve-sheath tumor seen with increased frequency in NF-1. In practice, the major distinction between a schwannoma and a solitary neurofibroma is that a schwannoma can be resected while sparing the underlying nerve, whereas resection of a neurofibroma requires the sacrifice of the underlying nerve.

Malignant peripheral nerve-sheath tumors (MPNST), once called neurofibrosarcomas, can arise from degeneration of a plexiform neurofibroma; this is, however, a rare complication. A plexiform neurofibromas has a lifetime risk of 8-12% of transformation.

Dermatologic manifestations

In addition to the cutaneous neurofibroma, patients with NF-1 develop flat pigmented lesions of the skin called café au lait spots.

NF-1 patients may also get freckles of the axillae (armpits). See Plexiform neurofibroma.

Central nervous system manifestations

The primary neurologic involvement is of the peripheral nervous system, as described above.

Intracranially, NF-1 patients have a predisposition to develop glial tumors of the central nervous system; primarily: optic gliomas and astrocytomas. Another CNS manifestation of NF-1 is the so-called "unidentified bright object" or UBO, which is a lesion which has increased signal on a T2 weighted sequence of a magnetic resonance imaging examination of the brain. These UBOs are typically found in the cerebellar peduncles, pons, midbrain, globus pallidus, thalamus, and optic radiations. Their exact identity remains a bit of a mystery since they disappear over time (usually, by age 16), and they are not typically biopsied or resected. They may represent a focally degenerative bit of myelin.

Within the CNS, this manifests as a weakness of the dura, which is the tough covering of the brain and spine. Weakness of the dura leads to focal enlargement (termed dural ectasia) due to chronic exposure to the pressures of CSF pulsation.

Radiographically, dural ectasia can lead to scalloping of the posterior vertebral bodies and to the formation of cystic diverticula of the dura of the spine (termed meningoceles).

Skeletal lesions

Bones, especially the ribs, can develop chronic erosions (pits) from the constant pressure of adjacent neurofibromas and schwannomas. Similarly, the neural foramen of the spine can be widened due to the presence of a nerve root neurofibroma or schwannoma.

In NF-1, these is also a generalized abnormality of the soft tissues, which is referred to as mesodermal dysplasia. This manifests as maldevelopment of skeletal structures, including

• Focal scoliosis and/or kyphosis, which is the most common skeletal manifestation of NF-1, occurring in 20% of affected patients. Approximately one quarter of patients will require corrective surgery.
• Bowing of a long bone with a tendency to fracture and not heal, yielding a pseudarthrosis. The most common bone to be affected is the tibia (causing congenital pseudarthrosis of the tibia or CPT). CPT occurs in 2-4% of individuals with NF-1.
• Malformation of the facial bones or of the eye sockets (lambdoid suture defects, sphenoid dysplasia)
• Unilateral overgrowth of a limb

Cognitive problems and learning disabilities in NF-1

The most common complication in patients with NF-1 is cognitive and learning disability. These cognitive problems have been shown to be present in approximately 80% of children with NF-1 and have significant effects on their schooling and everyday life. The most common cognitive problems are with perception, executive functioning and attention. ADHD has been shown to be present in approximately 38% of children with NF-1. Language, maths and motor deficits are also common. These cognitive problems have been shown to be stable into adulthood and do not get worse unlike some of the other physical symptoms of NF-1.

Diagnosis

The National Institute of Health (NIH) has created specific criteria for the diagnosis of NF-1. Two of these seven "Cardinal Clinical Features" are required for positive diagnosis.

• 6 or more café-au-lait macules over 5 mm in greatest diameter in pre-pubertal individuals and over 15 mm in greatest diameter in post-pubertal individuals
• 2 or more neurofibromas of any type or 1 plexiform neurofibroma
• Freckling in the axillary or inguinal regions
• Optic glioma
• 2 or more Lisch nodules (iris hamartomas)
• A distinctive osseous lesion such as sphenoid dysplasia or thinning of the long bone cortex with or without pseudarthrosis
• A first degree relative (parent, sibling, or offspring) with NF-1 by the above criteria

Prognosis

NF-1 is such a progressive and diverse condition that it makes it difficult to predict. The NF-1 gene manifest the disorder differently even amongst members of the same family. For example, some individuals have no symptoms, while others may have a manifestation that is rapidly more progressive and severe.

For many NF-1 patients, a primary concern is the disfigurement caused by cutaneous/dermal neurofibromas, pigmented lesions, and the occasional limb abnormalities.

However, there are many more severe complications caused by NF-1, but some of them are quite rare and they are listed in the following section.

Complications

• Chronic pain, numbness, Pritchetts face, and/or paralysis due to the peripheral nerve sheath tumors
• Blindness due to optic nerve gliomas
• Chronic hypertension from renal artery anomalies or pheochromocytoma, which patients with NF-1 are at increased risk of developing.
• Brain tumors
• Neurologic impairment due to severe spinal scoliosis and/or kyphosis, including but not limited to hydrocephalus
• Amputation due to a tibial pseudarthrosis
• Malignant degeneration of a plexiform neurofibroma into malignant peripheral nerve sheath tumor (MPNST), occurring in 8-12%
• Depression due to the shame of the disfigurement NF can cause to the body and face
• Social anxiety is also common among NF sufferers because of the reaction of others to the condition

Therapy

There is no cure for the disorder itself. Instead, people with neurofibromatosis are followed by a team of specialists to manage symptoms or complications. Surgery may be needed when the tumors compress organs or other structures. Less than 8-12% people with neurofibromatosis develop cancerous growths; in these cases, chemotherapy can be tried. There are several medical studies on NF-1. For more information, visit. This is the official website of the National Institute of Health. Currently testing 3 drugs to stop the growth of NF-1, more info on one called R115777 here.

These drugs are, simplistically, utilize novel farnesyl transferase inhibitors to inhibit the Ras kinase in a post translational modification step before the kinase pathway becomes hyperactive. The R115777 drug successfully passed phase one clinical trials but was suspended (NCT00029354) in phase two. Another drug, lovastatin is currently in phase one of clinical trials (NCT00352599).

Early research has shown potential for using the c-kit tyrosine kinase blocking properties of Imatinib in treatment of plexiform neurofibromas in neurofibromatosis type I.
 

The four cardinal patterns of peripheral neuropathy are polyneuropathy, mononeuropathy, mononeuritis multiplex and autonomic neuropathy. The most common form is (symmetrical) peripheral polyneuropathy, which mainly affects the feet and legs. The form of neuropathy may be further broken down by cause, or the size of predominant fiber involvement, i.e., large fiber or small fiber peripheral neuropathy. Frequently the cause of a neuropathy cannot be identified and it is designated idiopathic.

Neuropathy may be associated with varying combinations of weakness, autonomic changes and sensory changes. Loss of muscle bulk or fasciculations, a particular fine twitching of muscle may be seen. Sensory symptoms encompass loss of sensation and "positive" phenomena including pain. Symptoms depend on the type of nerves affected; motor, sensory, autonomic, and where the nerves are located in the body. One or more types of nerves may be affected. Common symptoms associated with damage to the motor nerve are muscle weakness, cramps, and spasms. Loss of balance and coordination may also occur. Damage to the sensory nerve can produce tingling, numbness, and pain. Pain associated with this nerve is described in various ways such as the following: sensation of wearing an invisible "glove" or "sock", burning, freezing, or electric-like, extreme sensitivity to touch. The autonomic nerve damage causes problems with involuntary functions leading to symptoms such as abnormal blood pressure and heart rate, reduced ability to perspire, constipation, bladder dysfunction (e.g., incontinence), and sexual dysfunction.

Causes

The causes are broadly grouped as follows:

• Genetic diseases: Friedreich's ataxia, Charcot-Marie-Tooth syndrome
• Metabolic/Endocrine: diabetes mellitus, chronic renal failure, porphyria, amyloidosis, liver failure, hypothyroidism
• Toxic causes: Drugs (vincristine, phenytoin, nitrofurantoin, isoniazid, ethyl alcohol), organic metals, heavy metals, excess intake of vitamin B6 (pyridoxine)
• Fluoroquinolone toxicity: Irreversible neuropathy is a serious adverse reaction of fluoroquinolone drugs
• Inflammatory diseases: Guillain-Barré syndrome, systemic lupus erythematosis, leprosy, Sjögren's syndrome
• Vitamin deficiency states: Vitamin B12 (cyanocobalamin), vitamin A, vitamin E, vitamin B1 (thiamin)
• Physical trauma: compression, pinching, cutting, projectile injuries (i.e. gunshot wound), strokes including prolonged occlusion of blood flow
• Others: shingles, malignant disease, HIV, radiation, chemotherapy

Many of the diseases of the peripheral nervous system may present similarly to muscle problems (myopathies), and so it is important to develop approaches for assessing sensory and motor disturbances in patients so that a physician may make an accurate diagnosis.

Types by pattern of nerve involvement

Mononeuropathy

Mononeuropathy is a type of neuropathy that only affects a single nerve. It is diagnostically useful to distinguish them from polyneuropathies, because the limitation in scope makes it more likely that the cause is a localized trauma or infection.

The commonest cause of mononeuropathy is by physical compression of the nerve, known as compression neuropathy. Carpal tunnel syndrome is one example of this. The "pins-and-needles" sensation of one's "foot falling asleep" (paresthesia) is caused by a compression mononeuropathy, albeit a temporary one which can be resolved merely by moving around and adjusting to a more appropriate position. Direct injury to a nerve, interruption of its blood supply (ischemia), or inflammation can also cause mononeuropathy.

Mononeuritis multiplex

Mononeuritis multiplex, or mononeuropathy multiplex, is the clinical result of damage to several different nerves, either serially or concurrently.

Mononeuritis multiplex typically presents with acute or subacute loss of sensory and motor function of individual peripheral nerves. The pattern of involvement is asymmetric.

Mononeuritis multiplex may also cause pain, which is characterized as deep, aching pain that is worse at night, is frequently in the lower back, hip, or leg. In people with diabetes mellitus, mononeuritis multiplex is typically encountered as acute, unilateral, severe thigh pain followed by anterior muscle weakness and loss of knee reflex.

Electrodiagnostic studies will show multifocal sensory motor axonal neuropathy.

It is caused by, or associated with, several medical conditions:

• diabetes mellitus
• vasculitides: polyarteritis nodosa, Wegener granulomatosis, and Churg-Strauss syndrome
• immune-mediated diseases like rheumatoid arthritis, lupus erythematosus (SLE), and sarcoidosis
• infections: leprosy, Lyme disease, HIV
• amyloidosis
• cryoglobulinemia
• chemical agents, including trichloroethylene and dapsone

Polyneuropathy

Polyneuropathy is a pattern of nerve damage which is quite different from mononeuropathy. The term "peripheral neuropathy" is sometimes used loosely to refer to polyneuropathy. In a polyneuropathy, many nerve cells in different parts of the body are affected, without regard to the nerve through which they pass. Not all nerve cells are affected in any particular case. In one common pattern (distal axonopathy), the cell bodies of neurons remain intact, but the axons are affected in proportion to their length. Diabetic neuropathy is the most common cause of this pattern. In demyelinating polyneuropathies, the myelin sheath around axons is damaged, which affects the ability of the axons to conduct electrical impulses. The third and least common pattern affects the cell bodies of neurones directly. This usually picks out either the motor neurones (known as motor neurone disease), or the sensory neurones (known as sensory neuronopathy or dorsal root ganglionopathy).

The effect of this is to cause symptoms in more than one part of the body, often on left and right sides symmetrically. As for any neuropathy, the chief symptoms include weakness or clumsiness of movement (motor); unusual or unpleasant sensations such as tingling or burning, reduction in the ability to feel texture, temperature etc., and impaired balance when standing or walking (sensory). In many polyneuropathies, these symptoms occur first and most severely in the feet. Autonomic symptoms may also occur, such as dizziness on standing up, erectile dysfunction and difficulty controlling urination.

Polyneuropathies are usually caused by processes that affect the body as a whole. Diabetes (or impaired glucose tolerance) is the most common cause. Other causes relate to the particular type of polyneuropathy, and there are many different causes of each type, including inflammatory diseases, vitamin deficiencies, blood disorders, and toxins (including alcohol and certain prescribed drugs). Most types of polyneuropathy progress fairly slowly, over months or years, but rapidly progressive polyneuropathy also occurs. Sometimes this has an identifiable cause; when it does not it is often referred to as Guillain–Barré syndrome. It is important to recognize that glucose levels in the blood can spike to nerve-damaging levels after eating even though fasting blood sugar levels and average blood glucose levels can still remain below normal levels (currently typically considered below 100 for FBP, Fasting Blood Plasma, and 6.0 for HGBA1c, hemoglobin A1C the test commonly used to measure average blood glucose levels over an extended period). Studies have shown that many of the cases of peripheral small fiber neuropathy with typical symptoms of tingling, pain and loss of sensation in the feet and hands are due to glucose intolerance prior to a diagnosis of diabetes or pre-diabetes. Such damage is often reversible, particularly in the early stages, with diet, exercise and weight loss.

The treatment of polyneuropathies is aimed firstly at eliminating or controlling the cause, secondly at maintaining muscle strength and physical function, and thirdly at controlling symptoms such as neuropathic pain.

Other classifications

Peripheral neuropathy may also be classified according to the type of nerve cell affected (motor, sensory, autonomic), or the process affecting the nerves (e.g. inflammation in neuritis).

Autonomic neuropathy

Autonomic neuropathy is a form of polyneuropathy which affects the non-voluntary, non-sensory nervous system (i.e. the autonomic nervous system) affecting mostly the internal organs such as the bladder muscles, the cardiovascular system, the digestive tract, and the genital organs. These nerves are not under a person's conscious control and function automatically. Autonomic nerve fibers form large collections in the thorax, abdomen and pelvis outside spinal cord, however they have connections with the spinal cord and ultimately the brain. Most commonly autonomic neuropathy is seen in persons with long-standing diabetes mellitus type 1 and 2. In most but not all cases, autonomic neuropathy occurs alongside other forms of neuropathy, such as sensory neuropathy.

Autonomic neuropathy is one cause of malfunction of the autonomic nervous system, but not the only one; some conditions affecting the brain or spinal cord can also cause autonomic dysfunction, such as multiple system atrophy, and therefore cause similar symptoms to autonomic neuropathy.

The signs and symptoms of autonomic neuropathy include the following:

• urinary bladder conditions: bladder incontinence or urine retention
• gastrointestinal tract: dysphagia, abdominal pain, nausea, vomiting, malabsorption, fecal incontinence, gastroparesis, diarrhea, constipation
• cardiovascular system: disturbances of heart rate (tachycardia, bradycardia), orthostatic hypotension, inadequate increase of heart rate on exertion
• other: hypoglycemia unawareness; genitalimpotence; sweat disturbances

Neuritis

Neuritis is a general term for inflammation of a nerve or the general inflammation of the peripheral nervous system. Symptoms depend on the nerves involved, but may include pain, paresthesia, paresis, hypoesthesia (numbness), anesthesia, paralysis, wasting, and disappearance of the reflexes. Causes include:

Infection:

• Herpes simplex
• Shingles
• Leprosy
• Guillain-Barre syndrome
• Chemical injury
• Physical injury
• Radiation

Underlying conditions causing localized neuritis (affecting a single nerve):

• Diphtheria
• Localized injury
• Diabetes

Underlying conditions causing polyneuritis (affecting multiple nerves):

• Beriberi
• Vitamin B12 deficiency
• Metabolic diseases
• Diabetes
• Hypothyroidism
• Porphyria
• Infections, bacterial and/or viral
• Autoimmune disease, especially Multiple Sclerosis
• Cancer
• Alcoholism
• Wartenbergs migratory sensory neuropathy

Types of neuritis include:

• Polyneuritis or Multiple neuritis (not to be confused with multiple sclerosis)
• Brachial neuritis
• Optic neuritis
• Vestibular neuritis
• Cranial neuritis, often representing as Bell's Palsy
• Arsenic neuritis

Signs and symptoms

Those with diseases or dysfunctions of their peripheral nerves can present with problems in any of the normal peripheral nerve functions.

In terms of sensory function, there are commonly loss of function (negative) symptoms, which include numbness, tremor, and gait imbalance.

Gain of function (positive) symptoms include tingling, pain, itching, crawling, and pins and needles. Pain can become intense enough to require use of opioid (narcotic) drugs (i.e., morphine, oxycodone).

Skin can become so hypersensitive that patients are prohibited from having anything touch certain parts of their body, especially the feet. People with this degree of sensitivity cannot have a bedsheet touch their feet or wear socks or shoes, and eventually become housebound.

Motor symptoms include loss of function (negative) symptoms of weakness, tiredness, heaviness, and gait abnormalities; and gain of function (positive) symptoms of cramps, tremor, and fasciculations.

There is also pain in the muscles (myalgia), cramps, etc., and there may also be autonomic dysfunction.

During physical examination, those with generalized peripheral neuropathies most commonly have distal sensory or motor and sensory loss, though those with a pathology (problem) of the peripheral nerves may be perfectly normal; may show proximal weakness, as in some inflammatory neuropathies like Guillain–Barré syndrome); or may show focal sensory disturbance or weakness, such as in mononeuropathies. Ankle jerk reflex is classically absent in peripheral neuropathy.

Treatment

Many treatment strategies for peripheral neuropathy are symptomatic. Some current research in animal models has shown that neurotrophin-3 can oppose the demyelination present in some peripheral neuropathies.

A range of drugs that act on the central nervous system such as drugs originally intended as antidepressants and antiepileptic drugs have been found to be useful in managing neuropathic pain. Commonly used treatments include using a Tricyclic antidepressant (such as amitriptyline) and antiepileptic therapies such as gabapentin or sodium valproate. These have the advantage that besides being effective in many cases they are relatively low cost.

A great deal of research has been done between 2005 and 2010 which indicates that synthetic cannabinoids and inhaled cannabis are effective treatments fo a range of neuropathic disorders. Research has demonstrated that the synthetic oral cannabinoid Nabilone is an effective adjunct treatment option for neuropathic conditions, especially for people who are resistant, tolerant, or allergic to common medications. Orally, opiate derivatives were found to be more effective than cannabis for most people. Smoked cannabis has been found to provide relief from HIV-associated sensory neuropathy. Smoked cannabis was also found to relieve neuropathy associated with CRPS type I, spinal chord injury, peripheral neuropathy, and nerve injury.

Pregabalin (INN) (pronounced /prɨˈgæbəlɨn/) is an anticonvulsant drug used for neuropathic pain. It has also been found effective for generalized anxiety disorder. It was designed as a more potent successor to gabapentin but is significantly more expensive, especially now the patent on gabapentin has expired and gabapentin is available as a generic drug. Pregabalin is marketed by Pfizer under the trade name Lyrica.

As noted above in the section on Polyneuropathies and their causes, symmetric small fiber neuropathy, commonly called peripheral neuropathy, can often be reversed, particularly in the early stages before a diagnosis of diabetes or pre-diabetes with diet, exercise and weight loss. It is also suggested that, because alcohol is a neurotoxin, even individuals with neuropathies from causes other than alcoholism may benefit from limiting or eliminating their alcohol intake.

TENS (Transcutaneous Electrical Nerve Stimulation) can be an effective in some cases as a non-pharmacological treatment and is free from adverse effects. It is believed to work via stimulating large afferent fibers, which in turn leads to an inhibition of small pain afferent fibers.
 

In medicine it is known as synchronous diaphragmatic flutter (SDF), or singultus, from the Latin singult, "the act of catching one's breath while sobbing". The hiccup is an involuntary action involving a reflex arc.

A bout of hiccups, in general, resolves itself without intervention, although many home remedies claim to shorten the duration, and medical treatment is occasionally necessary in cases of chronic hiccups.

Causes

Hiccups are caused by many central and peripheral nervous system disorders, all from injury or irritation to the phrenic and vagus nerves, as well as toxic or metabolic disorders affecting the aforementioned systems. Hiccups often occur after drinking carbonated beverages or alcohol. Prolonged laughter is also known to cause hiccups. Persistent or intractable hiccups may be caused by any condition which irritates or damages the relevant nerves. Chemotherapy—which can include a huge amount of different drugs—has been implicated in hiccups (some data states 30 percent of patients), while other studies have not proven such a relationship. Many times chemotherapy is applied to tumors sitting at places that are by themselves prone to cause hiccups, if irritated.

Phylogenetic hypothesis

Christian Straus and co-workers at the Respiratory Research Group, University of Calgary, Canada, propose that the hiccup is an evolutionary remnant of earlier amphibian respiration; amphibians such as frogs gulp air and water via a rather simple motor reflex akin to mammalian hiccuping. In support of this idea, they observe that the motor pathways that enable hiccuping form early during fetal development, before the motor pathways that enable normal lung ventilation to form; thus according to recapitulation theory the hiccup is evolutionarily antecedent to modern lung respiration. Additionally, they point out that hiccups and amphibian gulping are inhibited by elevated CO2 and can be completely stopped by the drug Baclofen (a GABAB receptor agonist), illustrating a shared physiology and evolutionary heritage. These proposals would explain why premature infants spend 2.5% of their time hiccuping, indeed they are gulping just like amphibians, as their lungs are not yet fully formed.

Treatment

Ordinary hiccups are cured easily without medical intervention; in most cases they can be stopped simply by forgetting about them. However, there are a number of anecdotal treatments for casual cases of hiccups. Some of the more common home remedies include giving the afflicted a fright or shock, eating peanut butter, taking a teaspoon of vinegar, drinking water (sometimes in an unorthodox manner), holding one's breath and altering one's breathing patterns. A solution involving sugar placed on or under the tongue was cited in the December 23, 1971 issue of the New England Journal of Medicine.

Medical treatment

Hiccups are treated medically only in severe and persistent (termed "intractable") cases, such as in the case of a 15-year-old girl who, in 2007, hiccuped continuously for five weeks. Haloperidol (Haldol, an anti-psychotic and sedative), metoclopramide (Reglan, a gastrointestinal stimulant), and chlorpromazine (Thorazine, an anti-psychotic with strong sedative effects) are used in cases of intractable hiccups. In severe or resistant cases, baclofen, an anti-spasmodic, is sometimes required to suppress hiccups. Effective treatment with sedatives often requires a dose that renders the person either unconscious or highly lethargic. Hence, medicating singultus is done short-term, as the affected individual cannot continue with normal life activities while taking the medication.

Digital rectal massage has been recommended as a remedy that causes immediate cessation of hiccups and which should be tried before resorting to drugs.

Persistent and intractable hiccups due to electrolyte imbalance (hypokalemia, hyponatremia) may benefit from drinking a carbonated beverage containing salt to normalize the potassium-sodium balance in the nervous system. The carbonation promotes quicker absorption. Carbonated beverages have though by themselves a tendency to provoke hiccup in some persons.

The administration of intranasal vinegar was found to ease the chronic and severe hiccups of a three-year old Japanese girl. Vinegar may stimulate the dorsal wall of the nasopharynx, where the pharyngeal branch of the glossopharyngeal nerve (the afferent of the hiccup reflex arc) is located.

Dr. Bryan R. Payne, a neurosurgeon at the Louisiana State University Health Sciences Center in New Orleans, has had some success with an experimental procedure in which a vagus nerve stimulator is implanted in the upper chest of patients with an intractable case of hiccups. "It sends rhythmic bursts of electricity to the brain by way of the vagus nerve, which passes through the neck. The Food and Drug Administration approved the vagus nerve stimulator in 1997 as a way to control seizures in some patients with epilepsy. In 2005, the agency endorsed the use of the stimulator as a treatment of last resort for people with severe depression".

Home remedies

While numerous home remedies are offered, they mostly fall into three broad categories: purely psychosomatic cures centered on relaxation and distraction, cures involving swallowing and eating (with the general rationale that this would remove irritants or reset mechanisms in the affected region).

Long-term cases

American man Charles Osborne had the hiccups for 68 years, from 1922 to 1990, and was entered in the Guinness World Records as the man with the Longest Attack of Hiccups.

In 2007, a teenager from Washington State in the United States named Cheyenne Motland hiccuped around 50 times a minute for more than five weeks. After her hiccups returned, her neurologist suggested that she may have Tourette syndrome, and the hiccups may be a "tic" caused by Tourette's.

Christopher Sands from the UK had hiccups for a period of almost three years which was eventually discovered to be due to a tumor located on the part of the brain that controls vascular activities, once 2/3 of the tumor was removed the hiccups appeared to settle and Sands no longer suffers from his condition.
 

The term “acoustic” is a misnomer, as the tumor rarely arises from the acoustic (or cochlear) division of the vestibulocochlear nerve. The term “neuroma” is also a misnomer, since it means “nerve tumor” but an acoustic neuroma is a Schwannoma. The correct medical term is vestibular schwannoma, because it involves the vestibular portion of the 8th cranial nerve and it arises from Schwann cells, which are responsible for the myelin sheath in the peripheral nervous system. Approximately 3,000 cases are diagnosed each year in the United States with a prevalence of about 1 in 100,000 worldwide. It compromises 5-10% of all intracranial neoplasms in adults. Incidence peaks in the fifth and sixth decades and both sexes are affected equally.

Pathogenesis

Acoustic neuromas may occur sporadically, or in some cases occur as part of von Recklinhausen neurofibromatosis, in which case the neuroma may take on one of two forms.

• In Neurofibromatosis type I, a schwannoma may sporadically involve the 8th nerve, usually in adult life, but may involve any other cranial nerve or the spinal root. Bilateral acoustic neuromas are rare in this type.
• In Neurofibromatosis type II, bilateral acoustic neuromas are the hallmark and typically present before the age of 21. These tumors tend to involve the entire extent of the nerve and show a strong autosomal dominant inheritance. Incidence is about 5 to 10%.

The usual tumor in the adult presents as a solitary tumor, originating in the nerve. It usually arises from the vestibular portion of the 8th nerve, just within the internal auditory canal. As the tumor grows, it usually extends into the posterior fossa to occupy the angle between the cerebellum and the pons (cerebellopontine angle). Because of its position, it may also compress the 5th, 7th, and less often, the 9th and 10th cranial nerves. Later, it may compress the pons and lateral medulla, causing obstruction of the cerebrospinal fluid and increased intracranial pressure.

Schwannomas can occur in relation to other cranial nerves or spinal nerve roots, resulting in radiculopathy or spinal cord compression. Trigeminal neuromas are the second most common form of schwannomas involving cranial nerves. Schwannomas of other cranial nerves are very rare.

Clinical manifestations

The earliest symptoms of acoustic neuromas include ipsilateral sensorineural hearing loss/deafness, disturbed sense of balance and altered gait, vertigo with associated nausea and vomiting, and pressure in the ear, all of which can be attributed to the disruption of normal vestibulocochlear nerve function. Additionally more than 80% of patients have reported tinnitus (most often a unilateral high-pitched ringing, sometimes a machinery-like roaring or hissing sound, like a steam kettle).

Large tumors that compress the adjacent brainstem may affect other local cranial nerves. Involvement of the nearby facial nerve (CN VII) may lead to ipsilateral facial weakness, sensory impairment, impairment of glandular secretions and loss of taste sensation in the anterior two-thirds of the tongue; involvement of the trigeminal nerve (CN V) may lead to loss of sensation in the involved side’s face and mouth. The glossopharyngeal and vagus nerves are uncommonly involved, but their involvement may lead to altered gag or swallowing reflexes.

Larger tumors may lead to increased intracranial pressure, with its associated symptoms such as headache, vomiting, and altered consciousness.

Diagnosis

Contrast-enhanced CT will detect almost all acoustic neuromas that are greater than 2.0 cm in diameter and project further than 1.5 cm into the cerebellopontine angle. Those tumors that are smaller may be detected by MRI with gadolinium enhancement. Audiology and vestibular tests should be concurrently evaluated using air conduction and bone conduction threshold testing to assess for sensorineural versus conduction hearing loss.

Treatment

Indicated treatments for acoustic neuroma include surgical removal and radiotherapy. About 25% of all acoustic neuromas are treated with medical management consisting of a periodic monitoring of the patient’s neurological status, serial imaging studies, and the use of hearing aids when appropriate.

Conservative treatment

Because these neuromata grow so slowly, a physician may opt for conservative treatment beginning with an observation period. In such a case, the tumor is monitored by annual MRI to monitor growth. This route is common among patients over 70 years old.  Records suggest that about 45% of acoustic neuromata do not grow detectably over the 3–5 years of observation. In rare cases, acoustical neuromata have been known to shrink spontaneously. Often people with acoustic neuromata die of other causes before the neuroma becomes life-threatening. (This is especially true of elderly people possessing a small neuroma.)

Since the growth rate of an acoustic neuroma rarely accelerates, annual observation is sufficient. Acoustic neuromata may cause either gradual or—less commonly—sudden hearing loss and tinnitus.

Surgery

Removal of acoustic neuromas may be performed using several approaches. Each approach has its advantages and disadvantages. Microsurgery for acoustic neuroma is the only technique that removes the tumor. Radiation treatment (discussed in another section) does not remove the tumor, but has the potential to slow or stop its growth. Surgery is the only treatment that will definitively treat balance symptoms associated with tumor growth, as the vestibular nerves are removed at surgery.

Surgery cannot repair damage that has already occurred to the facial or hearing nerves. Even after surgery, there is a small chance that the neuroma will grow back and follow-up MRI scans are necessary.

Choice of surgical approach is based on the patient’s age, medical condition, size of tumor, and preoperative hearing thresholds and speech discrimination, as well as other tests such as electronystagmography, imaging, and auditory brainstem response testing. The patient’s and surgeon’s preferences also play a significant role.

During removal of the tumor, the tumor along with the superior and inferior vestibular nerves are removed. This results in an acute loss of vestibular input to the brain from the operated side. However, vestibular function improves rapidly due to compensation by the other ear and other balance mechanisms.

Surgery carries risk to the facial nerve which may therefore be monitored during the procedure. Best results (normal or near normal facial function) are more likely with small acoustic neuromas.

Three surgical approaches are commonly used. The first is the translabyrinthine approach, which destroys hearing in the affected ear. Thus, it is often employed in patients who already have poor speech discrimination in the affected ear. Any size tumor may be removed with this approach. There is no brain retraction with this approach, so it is often considered the safest route to remove the tumor. In patients with neurofibromatosis type 2 who undergo auditory brainstem implantation, this technique is used as it provides the most direct path of access to the lateral recess and cochlear nucleus, where the device is placed.

The two other approaches (suboccipital retrosigmoid and middle fossa) are hearing preservation approaches, which have a chance of preserving some or all of the hearing in the affected ear. Neurosurgeons often prefer the retrosigmoid approach, as they are frequently more familiar with it from training.

The middle fossa approach is used for tumors typically less than 2 cm in greatest dimension, where hearing conservation is to be attempted. This approach has the advantage over the retrosigmoid approach in its direct access to the lateral end of the internal auditory canal. Multiple reports have shown that the retrosigmoid approach cannot reach the lateral end of the internal auditory canal without violating the posterior semicircular canal, and hence destroying the hearing.

A less common approach is minimally invasive endoscopic surgery. This approach is available in specialized centers.

Acoustic neuroma surgery is highly technically demanding. It may be performed by neurosurgeons alone or together with an otolaryngologist.

Radiation therapy

Radiation therapy is done in a variety of ways, but mainly by three methods: gamma knife radiosurgery or fractionated stereotactic radiotherapy, with a Linear Accelerator (Linac) or Proton therapy^[5]. In the gamma knife approach, 201 beams of gamma radiation are focused on the tumor in a single session. The damage to the tumor at the convergence point may cause it to stop growing but usually does not cause it to shrink in the long term. It may cause short-term shrinkage due to necrosis in the tumor. The damage may be to the tumor cells and/or to the tumor vasculature.

It is not clear what percentage of tumors are controlled by this method for long periods. In earlier times when higher radiation doses were used, the failure rate was about 12% (which then required surgery). Most surgeons feel that these tumors are much more difficult to remove after radiation treatment. Radiation does not remove the tumor, and when irradiated tumors are surgically removed, it is often found that they have growing tumor cells in them.

Two risks of radiation treatment are carcinogenic progression of the acoustic neuroma (conversion from benign to malignant) or induction of other tumors (such as glioblastoma) in the nearby irradiated brain tissue. The incidence of these events appears to be low, and it is often said to be one in one thousand or less. (However, the incidence is markedly higher in patients with neurofibromatosis type 2.) This calculation is done by dividing the number of obvious cases of tumorigenic progression or secondary tumor reported in the medical literature by the estimated number of gamma knife procedures done in the world to date. This is not a scientifically valid method of estimating the carcinogenic risk of medical radiation exposures, and involves a list of very questionable assumptions.

The proper and scientifically valid way to estimate such risks can be found at the web site of the Health Physics Society, where estimates of the risks of CT scans and other procedures can be found. These calculations have never been made for gamma knife radiosurgery.

Due to the possibility of regrowth and the possibility of tumorigenic progression or secondary tumors, it is essential that radiation treatments for acoustic neuromas be followed by yearly MRI for the rest of the patient’s life. MRIs at this time (2007) cost between $1,500-$3,000. Long-term secondary effects (for instance cognitive effects) on a scale of 10–20 years are not yet established for gamma knife surgery.

Fractionated stereotactic therapy involves a beam of ionizing radiation focused on the tumor from a moving gantry. The beam is wider and less accurate than that of the gamma knife. The total dose is also much higher than that used in gamma knife radiosurgery, but the fractionation of the dose (done on many different days) spares normal tissue. This method has not been done on as many patients as gamma knife procedures and there have not been as many years of follow-up study. This means that the tumor control by this method is not yet established, and the incidence of secondary effects of the radiation are not yet known. There are a number of variations on the Linac machine, which can confuse patients. The best known are the “Peacock” which is essentially a modified collimator, and the Cyberknife which uses a miniature Linac machine attached to a robot arm which is guided using x-ray imaging to check the position of the patient between each treatment shot.

A Proton therapy machine uses a beam of protons to kill the tumour and a Cyclotron is used to generate the beam. Theoretically, this is preferable to the x-rays used by the Linac and Gamma Knife machines as the protons can, in theory, be stopped before they exit the tumor, thus reducing damage to normal tissue. However, to date, very few people have been treated by this method and the results known are not statistically good.