Neurosarcoidosis
Encyclopedia
Neurosarcoidosis refers to sarcoidosis
, a condition of unknown cause featuring granuloma
s in various tissues, involving the central nervous system
(brain and spinal cord). It can have many manifestations, but abnormalities of the cranial nerves
(a group of twelve nerves supplying the head and neck area) are the most common. It may develop acutely, subacutely, and chronically. Approximately 5-10% of people with sarcoidosis of other organs (e.g. lung
) develop central nervous system involvement. Only 1% of people with sarcoidosis will have neurosarcoidosis alone without involvement of any other organs. Diagnosis can be difficult, with no test apart from biopsy
being completely reliable. Treatment is with immunosuppression
. The first case of sarcoidosis involving the nervous system was reported in 1948.
, which may lead to reduced power on one or both sides of the face (65% resp 35% of all cranial nerve cases), followed by reduction in visual perception
due to optic nerve
involvement. Rarer symptoms are double vision
(oculomotor nerve
, trochlear nerve
or abducens nerve), decreased sensation of the face (trigeminal nerve
), hearing loss or vertigo
(vestibulocochlear nerve
), swallowing problems
(glossopharyngeal nerve
) and weakness of the shoulder muscles (accessory nerve
) or the tongue
(hypoglossal nerve
). Visual problems may also be the result of papilledema
(swelling of the optic disc
) due to obstruction by granulomas of the normal cerebrospinal fluid
(CSF) circulation.
Seizure
s (mostly of the tonic-clonic
/"grand mal" type) are present in about 15%, and may be the presenting phenomenon in 10%.
Meningitis
(inflammation of the lining of the brain) occurs in 3-26% of cases. Symptoms may include headache
and nuchal rigidity
(being unable to bend the head forward). It may be acute or chronic.
Accumulation of granulomas in particular areas of the brain can lead to abnormalities in the function of that area. For instance, involvement of the internal capsule
would lead to weakness in one or two limbs on one side of the body. If the granulomas are large, they can exert a mass effect and cause headache
and increase the risk of seizures. Obstruction of the flow of cerebrospinal fluid, too, can cause headaches, visual symptoms (as mentioned above) and other features of raised intracranial pressure
and hydrocephalus
Involvement of the spinal cord
is rare, but can lead to abnormal sensation or weakness in one or more limbs, or cauda equina
symptoms (incontinence to urine
or stool
, decreased sensation in the buttocks).
, which produces numerous hormone
s, is rare but leads to any of the symptoms of hypopituitarism
: amenorrhoea
(cessation of the menstrual cycle
), diabetes insipidus
(dehydration due to inability to concentrate the urine), hypothyroidism
(decreased activity of the thyroid
) or hypocortisolism (deficiency of cortisol
).
occur in 20% of cases; many different disorders have been reported, e.g. depression
and psychosis
. Peripheral neuropathy
has been reported in up to 15% of cases of neurosarcoidosis.
Other symptoms due to sarcoidosis of other organs may be uveitis
(inflammation of the uveal layer
in the eye), dyspnoea (shortness of breath), arthralgia
(joint pains), lupus pernio
(a red skin rash, usually of the face), erythema nodosum
(red skin lumps, usually on the shins), and symptoms of liver
involvement (jaundice
) or heart
involvement (heart failure).
(surgically removing a tissue sample). Because of the risks associated with brain biopsies, they are avoided as much as possible. Other investigations that may be performed in any of the symptoms mentioned above are computed tomography
(CT) or magnetic resonance imaging
(MRI) of the brain, lumbar puncture
, electroencephalography
(EEG) and evoked potential
(EP) studies. If the diagnosis of sarcoidosis is suspected, typical X-ray
or CT appearances of the chest may make the diagnosis more likely; elevations in angiotensin-converting enzyme
and calcium
in the blood, too, make sarcoidosis more likely. In the past, the Kveim test
was used to diagnose sarcoidosis. This now obsolete test had a high (85%) sensitivity, but required spleen
tissue of a known sarcoidosis patient, an extract of which was injected into the skin of a suspected case.
Only biopsy of suspicious lesions in the brain or elsewhere is considered useful for a definitive diagnosis of neurosarcoid. This would demonstrate granuloma
s (collections of inflammatory cells) rich in epithelioid
cells and surrounded by other immune system cells (e.g. plasma cell
s, mast cell
s). Biopsy may be performed to distinguish mass lesions from tumours (e.g. glioma
s).
MRI with gadolinium
enhancement is the most useful neuroimaging test. This may show enhancement of the pia mater
or white matter
lesions that may resemble the lesions seen in multiple sclerosis
.
Lumbar puncture may demonstrate raised protein
level, pleiocytosis (i.e. increased presence of both lymphocyte
s and neutrophil granulocyte
s) and oligoclonal band
s. Various other tests (e.g. ACE level in CSF) have little added value.
, may have a particular precipitant and have a specific course. It is unknown which characteristics predispose sarcoidosis patients to brain or spinal cord involvement.
s such as prednisolone
. If this is effective, the dose may gradually be reduced (although many patients need to remain on steroids long-term, frequently leading to side-effects such as diabetes
or osteoporosis
). Methotrexate
, hydroxychloroquine
, cyclophosphamide
, pentoxifylline, thalidomide
and infliximab
have been reported to be effective in small studies. In patients unresponsive to medical treatment, radiotherapy
may be required. If the granulomatous tissue causes obstruction or mass effect, neurosurgical
intervention is sometimes necessary. Seizures can be prevented with anticonvulsant
s, and psychiatric phenomena may be treated with medication usually employed in these situations.
involvement is known to have a good prognosis and good response to treatment. Long-term treatment is usually necessary for all other phenomena.
wrote "Model Patient: My Life As an Incurable Wise-Ass" on her experiences with neurosarcoidosis.
Sarcoidosis
Sarcoidosis , also called sarcoid, Besnier-Boeck disease or Besnier-Boeck-Schaumann disease, is a disease in which abnormal collections of chronic inflammatory cells form as nodules in multiple organs. The cause of sarcoidosis is unknown...
, a condition of unknown cause featuring granuloma
Granuloma
Granuloma is a medical term for a tiny collection of immune cells known as macrophages. Granulomas form when the immune system attempts to wall off substances that it perceives as foreign but is unable to eliminate. Such substances include infectious organisms such as bacteria and fungi as well as...
s in various tissues, involving the central nervous system
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
(brain and spinal cord). It can have many manifestations, but abnormalities of the cranial nerves
Cranial nerves
Cranial nerves are nerves that emerge directly from the brain, in contrast to spinal nerves, which emerge from segments of the spinal cord. In humans, there are traditionally twelve pairs of cranial nerves...
(a group of twelve nerves supplying the head and neck area) are the most common. It may develop acutely, subacutely, and chronically. Approximately 5-10% of people with sarcoidosis of other organs (e.g. lung
Lung
The lung is the essential respiration organ in many air-breathing animals, including most tetrapods, a few fish and a few snails. In mammals and the more complex life forms, the two lungs are located near the backbone on either side of the heart...
) develop central nervous system involvement. Only 1% of people with sarcoidosis will have neurosarcoidosis alone without involvement of any other organs. Diagnosis can be difficult, with no test apart from biopsy
Biopsy
A biopsy is a medical test involving sampling of cells or tissues for examination. It is the medical removal of tissue from a living subject to determine the presence or extent of a disease. The tissue is generally examined under a microscope by a pathologist, and can also be analyzed chemically...
being completely reliable. Treatment is with immunosuppression
Immunosuppression
Immunosuppression involves an act that reduces the activation or efficacy of the immune system. Some portions of the immune system itself have immuno-suppressive effects on other parts of the immune system, and immunosuppression may occur as an adverse reaction to treatment of other...
. The first case of sarcoidosis involving the nervous system was reported in 1948.
Neurological
Abnormalities of the cranial nerves are present 50-70% of cases. The most common abnormality is involvement of the facial nerveFacial nerve
The facial nerve is the seventh of twelve paired cranial nerves. It emerges from the brainstem between the pons and the medulla, and controls the muscles of facial expression, and functions in the conveyance of taste sensations from the anterior two-thirds of the tongue and oral cavity...
, which may lead to reduced power on one or both sides of the face (65% resp 35% of all cranial nerve cases), followed by reduction in visual perception
Visual perception
Visual perception is the ability to interpret information and surroundings from the effects of visible light reaching the eye. The resulting perception is also known as eyesight, sight, or vision...
due to optic nerve
Optic nerve
The optic nerve, also called cranial nerve 2, transmits visual information from the retina to the brain. Derived from the embryonic retinal ganglion cell, a diverticulum located in the diencephalon, the optic nerve doesn't regenerate after transection.-Anatomy:The optic nerve is the second of...
involvement. Rarer symptoms are double vision
Diplopia
Diplopia, commonly known as double vision, is the simultaneous perception of two images of a single object that may be displaced horizontally, vertically, or diagonally in relation to each other...
(oculomotor nerve
Oculomotor nerve
The oculomotor nerve is the 3rd of 12 paired cranial nerves. It enters the orbit via the superior orbital fissure and controls most of the eye's movements, including constriction of the pupil and maintaining an open eyelid by innervating the Levator palpebrae superiors muscle. The optic nerve is...
, trochlear nerve
Trochlear nerve
The trochlear nerve is a motor nerve that innervates a single muscle: the superior oblique muscle of the eye....
or abducens nerve), decreased sensation of the face (trigeminal nerve
Trigeminal nerve
The trigeminal nerve contains both sensory and motor fibres. It is responsible for sensation in the face and certain motor functions such as biting, chewing, and swallowing. Sensory information from the face and body is processed by parallel pathways in the central nervous system...
), hearing loss or vertigo
Vertigo (medical)
Vertigo is a type of dizziness, where there is a feeling of motion when one is stationary. The symptoms are due to a dysfunction of the vestibular system in the inner ear...
(vestibulocochlear nerve
Vestibulocochlear nerve
The vestibulocochlear nerve is the eighth of twelve cranial nerves, and is responsible for transmitting sound and equilibrium information from the inner ear to the brain...
), swallowing problems
Dysphagia
Dysphagia is the medical term for the symptom of difficulty in swallowing. Although classified under "symptoms and signs" in ICD-10, the term is sometimes used as a condition in its own right. Sufferers are sometimes unaware of their dysphagia....
(glossopharyngeal nerve
Glossopharyngeal nerve
The glossopharyngeal nerve is the ninth of twelve pairs of cranial nerves . It exits the brainstem out from the sides of the upper medulla, just rostral to the vagus nerve...
) and weakness of the shoulder muscles (accessory nerve
Accessory nerve
In anatomy, the accessory nerve is a nerve that controls specific muscles of the shoulder and neck. As part of it was formerly believed to originate in the brain, it is considered a cranial nerve...
) or the tongue
Tongue
The tongue is a muscular hydrostat on the floors of the mouths of most vertebrates which manipulates food for mastication. It is the primary organ of taste , as much of the upper surface of the tongue is covered in papillae and taste buds. It is sensitive and kept moist by saliva, and is richly...
(hypoglossal nerve
Hypoglossal nerve
The hypoglossal nerve is the twelfth cranial nerve , leading to the tongue. The nerve arises from the hypoglossal nucleus and emerges from the medulla oblongata in the preolivary sulcus separating the olive and the pyramid. It then passes through the hypoglossal canal...
). Visual problems may also be the result of papilledema
Papilledema
Papilledema is optic disc swelling that is caused by increased intracranial pressure. The swelling is usually bilateral and can occur over a period of hours to weeks. Unilateral presentation is extremely rare....
(swelling of the optic disc
Optic disc
The optic disc or optic nerve head is the location where ganglion cell axons exit the eye to form the optic nerve. There are no light sensitive rods or cones to respond to a light stimulus at this point. This causes a break in the visual field called "the blind spot" or the "physiological blind spot"...
) due to obstruction by granulomas of the normal cerebrospinal fluid
Cerebrospinal fluid
Cerebrospinal fluid , Liquor cerebrospinalis, is a clear, colorless, bodily fluid, that occupies the subarachnoid space and the ventricular system around and inside the brain and spinal cord...
(CSF) circulation.
Seizure
Seizure
An epileptic seizure, occasionally referred to as a fit, is defined as a transient symptom of "abnormal excessive or synchronous neuronal activity in the brain". The outward effect can be as dramatic as a wild thrashing movement or as mild as a brief loss of awareness...
s (mostly of the tonic-clonic
Tonic-clonic seizure
Tonic–clonic seizures are a type of generalized seizure that affects the entire brain...
/"grand mal" type) are present in about 15%, and may be the presenting phenomenon in 10%.
Meningitis
Meningitis
Meningitis is inflammation of the protective membranes covering the brain and spinal cord, known collectively as the meninges. The inflammation may be caused by infection with viruses, bacteria, or other microorganisms, and less commonly by certain drugs...
(inflammation of the lining of the brain) occurs in 3-26% of cases. Symptoms may include headache
Headache
A headache or cephalalgia is pain anywhere in the region of the head or neck. It can be a symptom of a number of different conditions of the head and neck. The brain tissue itself is not sensitive to pain because it lacks pain receptors. Rather, the pain is caused by disturbance of the...
and nuchal rigidity
Meningism
Meningism is the triad of nuchal rigidity , photophobia and headache. It is a sign of irritation of the meninges, such as seen in meningitis, subarachnoid hemorrhages and various other diseases...
(being unable to bend the head forward). It may be acute or chronic.
Accumulation of granulomas in particular areas of the brain can lead to abnormalities in the function of that area. For instance, involvement of the internal capsule
Internal capsule
The internal capsule is an area of white matter in the brain that separates the caudate nucleus and the thalamus from the lenticular nucleus. The internal capsule contains both ascending and descending axons....
would lead to weakness in one or two limbs on one side of the body. If the granulomas are large, they can exert a mass effect and cause headache
Headache
A headache or cephalalgia is pain anywhere in the region of the head or neck. It can be a symptom of a number of different conditions of the head and neck. The brain tissue itself is not sensitive to pain because it lacks pain receptors. Rather, the pain is caused by disturbance of the...
and increase the risk of seizures. Obstruction of the flow of cerebrospinal fluid, too, can cause headaches, visual symptoms (as mentioned above) and other features of raised intracranial pressure
Intracranial pressure
Intracranial pressure is the pressure inside the skull and thus in the brain tissue and cerebrospinal fluid . The body has various mechanisms by which it keeps the ICP stable, with CSF pressures varying by about 1 mmHg in normal adults through shifts in production and absorption of CSF...
and hydrocephalus
Hydrocephalus
Hydrocephalus , also known as "water in the brain," is a medical condition in which there is an abnormal accumulation of cerebrospinal fluid in the ventricles, or cavities, of the brain. This may cause increased intracranial pressure inside the skull and progressive enlargement of the head,...
Involvement of the spinal cord
Spinal cord
The spinal cord is a long, thin, tubular bundle of nervous tissue and support cells that extends from the brain . The brain and spinal cord together make up the central nervous system...
is rare, but can lead to abnormal sensation or weakness in one or more limbs, or cauda equina
Cauda equina
The cauda equina is a structure within the lower end of the spinal column of most vertebrates, that consists of nerve roots and rootlets from above...
symptoms (incontinence to urine
Urinary incontinence
Urinary incontinence is any involuntary leakage of urine. It is a common and distressing problem, which may have a profound impact on quality of life. Urinary incontinence almost always results from an underlying treatable medical condition but is under-reported to medical practitioners...
or stool
Fecal incontinence
Fecal incontinence is the loss of regular control of the bowels. Involuntary excretion and leaking are common occurrences for those affected. Subjects relating to defecation are often socially unacceptable, thus those affected may be beset by feelings of shame and humiliation...
, decreased sensation in the buttocks).
Endocrine
Granulomas in the pituitary glandPituitary gland
In vertebrate anatomy the pituitary gland, or hypophysis, is an endocrine gland about the size of a pea and weighing 0.5 g , in humans. It is a protrusion off the bottom of the hypothalamus at the base of the brain, and rests in a small, bony cavity covered by a dural fold...
, which produces numerous hormone
Hormone
A hormone is a chemical released by a cell or a gland in one part of the body that sends out messages that affect cells in other parts of the organism. Only a small amount of hormone is required to alter cell metabolism. In essence, it is a chemical messenger that transports a signal from one...
s, is rare but leads to any of the symptoms of hypopituitarism
Hypopituitarism
Hypopituitarism is the decreased secretion of one or more of the eight hormones normally produced by the pituitary gland at the base of the brain...
: amenorrhoea
Amenorrhoea
Amenorrhoea , amenorrhea , or amenorrhœa, is the absence of a menstrual period in a woman of reproductive age. Physiological states of amenorrhoea are seen during pregnancy and lactation , the latter also forming the basis of a form of contraception known as the lactational amenorrhoea method...
(cessation of the menstrual cycle
Menstrual cycle
The menstrual cycle is the scientific term for the physiological changes that can occur in fertile women for the purpose of sexual reproduction. This article focuses on the human menstrual cycle....
), diabetes insipidus
Diabetes insipidus
Diabetes insipidus is a condition characterized by excessive thirst and excretion of large amounts of severely diluted urine, with reduction of fluid intake having no effect on the concentration of the urine. There are several different types of DI, each with a different cause...
(dehydration due to inability to concentrate the urine), hypothyroidism
Hypothyroidism
Hypothyroidism is a condition in which the thyroid gland does not make enough thyroid hormone.Iodine deficiency is the most common cause of hypothyroidism worldwide but it can be caused by other causes such as several conditions of the thyroid gland or, less commonly, the pituitary gland or...
(decreased activity of the thyroid
Thyroid
The thyroid gland or simply, the thyroid , in vertebrate anatomy, is one of the largest endocrine glands. The thyroid gland is found in the neck, below the thyroid cartilage...
) or hypocortisolism (deficiency of cortisol
Cortisol
Cortisol is a steroid hormone, more specifically a glucocorticoid, produced by the adrenal gland. It is released in response to stress and a low level of blood glucocorticoids. Its primary functions are to increase blood sugar through gluconeogenesis; suppress the immune system; and aid in fat,...
).
Mental and other
Psychiatric problemsPsychiatry
Psychiatry is the medical specialty devoted to the study and treatment of mental disorders. These mental disorders include various affective, behavioural, cognitive and perceptual abnormalities...
occur in 20% of cases; many different disorders have been reported, e.g. depression
Clinical depression
Major depressive disorder is a mental disorder characterized by an all-encompassing low mood accompanied by low self-esteem, and by loss of interest or pleasure in normally enjoyable activities...
and psychosis
Psychosis
Psychosis means abnormal condition of the mind, and is a generic psychiatric term for a mental state often described as involving a "loss of contact with reality"...
. Peripheral neuropathy
Peripheral neuropathy
Peripheral neuropathy is the term for damage to nerves of the peripheral nervous system, which may be caused either by diseases of or trauma to the nerve or the side-effects of systemic illness....
has been reported in up to 15% of cases of neurosarcoidosis.
Other symptoms due to sarcoidosis of other organs may be uveitis
Uveitis
Uveitis specifically refers to inflammation of the middle layer of the eye, termed the "uvea" but in common usage may refer to any inflammatory process involving the interior of the eye....
(inflammation of the uveal layer
Uvea
The uvea , also called the uveal layer, uveal coat, uveal tract, or vascular tunic, is the pigmented middle of the three concentric layers that make up an eye. The name is possibly a reference to its reddish-blue or almost black colour, wrinkled appearance and grape-like size and shape when...
in the eye), dyspnoea (shortness of breath), arthralgia
Arthralgia
Arthralgia literally means joint pain; it is a symptom of injury, infection, illnesses or an allergic reaction to medication....
(joint pains), lupus pernio
Lupus pernio
Lupus pernio is a chronic raised indurated lesion of the skin, often purplish in color. It resembles frostbite as it is seen on ears, cheeks, lips, nose, hands, fingers and forehead. It is pathognomonic of sarcoidosis. Microscopically, it resembles lupus vulgaris...
(a red skin rash, usually of the face), erythema nodosum
Erythema nodosum
Erythema nodosum is an inflammation of the fat cells under the skin characterized by tender red nodules or lumps that are usually seen on both shins...
(red skin lumps, usually on the shins), and symptoms of liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
involvement (jaundice
Jaundice
Jaundice is a yellowish pigmentation of the skin, the conjunctival membranes over the sclerae , and other mucous membranes caused by hyperbilirubinemia . This hyperbilirubinemia subsequently causes increased levels of bilirubin in the extracellular fluid...
) or heart
Heart
The heart is a myogenic muscular organ found in all animals with a circulatory system , that is responsible for pumping blood throughout the blood vessels by repeated, rhythmic contractions...
involvement (heart failure).
Diagnosis
The diagnosis of neurosarcoidosis often is difficult. Definitive diagnosis can only be made by biopsyBiopsy
A biopsy is a medical test involving sampling of cells or tissues for examination. It is the medical removal of tissue from a living subject to determine the presence or extent of a disease. The tissue is generally examined under a microscope by a pathologist, and can also be analyzed chemically...
(surgically removing a tissue sample). Because of the risks associated with brain biopsies, they are avoided as much as possible. Other investigations that may be performed in any of the symptoms mentioned above are computed tomography
Computed tomography
X-ray computed tomography or Computer tomography , is a medical imaging method employing tomography created by computer processing...
(CT) or magnetic resonance imaging
Magnetic resonance imaging
Magnetic resonance imaging , nuclear magnetic resonance imaging , or magnetic resonance tomography is a medical imaging technique used in radiology to visualize detailed internal structures...
(MRI) of the brain, lumbar puncture
Lumbar puncture
A lumbar puncture is a diagnostic and at times therapeutic procedure that is performed in order to collect a sample of cerebrospinal fluid for biochemical, microbiological, and cytological analysis, or very rarely as a treatment to relieve increased intracranial pressure.-Indications:The...
, electroencephalography
Electroencephalography
Electroencephalography is the recording of electrical activity along the scalp. EEG measures voltage fluctuations resulting from ionic current flows within the neurons of the brain...
(EEG) and evoked potential
Evoked potential
An evoked potential is an electrical potential recorded from the nervous system of a human or other animal following presentation of a stimulus, as distinct from spontaneous potentials as detected by electroencephalography or electromyography .Evoked potential amplitudes tend to be low, ranging...
(EP) studies. If the diagnosis of sarcoidosis is suspected, typical X-ray
Chest X-ray
In medicine, a chest radiograph, commonly called a chest X-ray , is a projection radiograph of the chest used to diagnose conditions affecting the chest, its contents, and nearby structures...
or CT appearances of the chest may make the diagnosis more likely; elevations in angiotensin-converting enzyme
Angiotensin-converting enzyme
Angiotensin I-converting enzyme , an exopeptidase, is a circulating enzyme that participates in the body's renin-angiotensin system , which mediates extracellular volume , and arterial vasoconstriction...
and calcium
Calcium in biology
Calcium plays a pivotal role in the physiology and biochemistry of organisms and the cell. It plays an important role in signal transduction pathways, where it acts as a second messenger, in neurotransmitter release from neurons, contraction of all muscle cell types, and fertilization...
in the blood, too, make sarcoidosis more likely. In the past, the Kveim test
Kveim test
The Kveim test, Nickerson-Kveim or Kveim-Siltzbach test is a skin test used to detect sarcoidosis, where part of a spleen from a patient with known sarcoidosis is injected into the skin of a patient suspected to have the disease. If granulomas are found , the test is positive. If the patient has...
was used to diagnose sarcoidosis. This now obsolete test had a high (85%) sensitivity, but required spleen
Spleen
The spleen is an organ found in virtually all vertebrate animals with important roles in regard to red blood cells and the immune system. In humans, it is located in the left upper quadrant of the abdomen. It removes old red blood cells and holds a reserve of blood in case of hemorrhagic shock...
tissue of a known sarcoidosis patient, an extract of which was injected into the skin of a suspected case.
Only biopsy of suspicious lesions in the brain or elsewhere is considered useful for a definitive diagnosis of neurosarcoid. This would demonstrate granuloma
Granuloma
Granuloma is a medical term for a tiny collection of immune cells known as macrophages. Granulomas form when the immune system attempts to wall off substances that it perceives as foreign but is unable to eliminate. Such substances include infectious organisms such as bacteria and fungi as well as...
s (collections of inflammatory cells) rich in epithelioid
Epithelioid
An epithelioid cell is a cell that resembles epithelial cells in that it directly contacts its neighboring cells via cell surface molecules or junctions. Unlike epithelial cells, however, epithelioid cells make contacts over their entire surface, rather than at restricted portions. The term...
cells and surrounded by other immune system cells (e.g. plasma cell
Plasma cell
Plasma cells, also called plasma B cells, plasmocytes, and effector B cells, are white blood cells which produce large volumes of antibodies. They are transported by the blood plasma and the lymphatic system...
s, mast cell
Mast cell
A mast cell is a resident cell of several types of tissues and contains many granules rich in histamine and heparin...
s). Biopsy may be performed to distinguish mass lesions from tumours (e.g. glioma
Glioma
A glioma is a type of tumor that starts in the brain or spine. It is called a glioma because it arises from glial cells. The most common site of gliomas is the brain.-By type of cell:...
s).
MRI with gadolinium
Gadolinium
Gadolinium is a chemical element with the symbol Gd and atomic number 64. It is a silvery-white, malleable and ductile rare-earth metal. It is found in nature only in combined form. Gadolinium was first detected spectroscopically in 1880 by de Marignac who separated its oxide and is credited with...
enhancement is the most useful neuroimaging test. This may show enhancement of the pia mater
Pia mater
Pia mater often referred to as simply the pia, is the delicate innermost layer of the meninges, the membranes surrounding the brain and spinal cord. The word finds its roots in Latin, meaning literally "tender mother." The other two meningeal membranes are the dura mater and the arachnoid mater....
or white matter
White matter
White matter is one of the two components of the central nervous system and consists mostly of myelinated axons. White matter tissue of the freshly cut brain appears pinkish white to the naked eye because myelin is composed largely of lipid tissue veined with capillaries. Its white color is due to...
lesions that may resemble the lesions seen in multiple sclerosis
Multiple sclerosis
Multiple sclerosis is an inflammatory disease in which the fatty myelin sheaths around the axons of the brain and spinal cord are damaged, leading to demyelination and scarring as well as a broad spectrum of signs and symptoms...
.
Lumbar puncture may demonstrate raised protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
level, pleiocytosis (i.e. increased presence of both lymphocyte
Lymphocyte
A lymphocyte is a type of white blood cell in the vertebrate immune system.Under the microscope, lymphocytes can be divided into large lymphocytes and small lymphocytes. Large granular lymphocytes include natural killer cells...
s and neutrophil granulocyte
Neutrophil granulocyte
Neutrophil granulocytes are the most abundant type of white blood cells in mammals and form an essential part of the innate immune system. They are generally referred to as either neutrophils or polymorphonuclear neutrophils , and are subdivided into segmented neutrophils and banded neutrophils...
s) and oligoclonal band
Oligoclonal band
Oligoclonal bands are bands of immunoglobulins that are seen when a patient's blood serum, gained from blood plasma, or cerebrospinal fluid is analyzed....
s. Various other tests (e.g. ACE level in CSF) have little added value.
Criteria
Some recent papers propose to classify neurosarcoidosis by likelihood:- Definite neurosarcoidosis can only be diagnosed by plausible symptoms, a positive biopsy and no other possible causes for the symptoms
- Probable neurosarcoidosis can be diagnosed if the symptoms are suggestive, there is evidence of central nervous system inflammation (e.g. CSF and MRI), and other diagnoses have been excluded. A diagnosis of systemic sarcoidosis is not essential.
- Possible neurosarcoidosis may be diagnosed if there are symptoms not due to other conditions but other criteria are not fulfilled.
Pathophysiology
Sarcoidosis is a disease of unknown cause that leads to the development of granulomas in various organs. While the lungs are typically involved, other organs may equally be affected. Some subforms of sarcoidosis, such as Löfgren syndromeLöfgren syndrome
Löfgren syndrome is a type of acute sarcoidosis that is frequent in Scandinavian, Irish, African and Puerto Rican women.It was characterized in 1953.Some have considered the condition to be imprecisely defined.-Presentation:...
, may have a particular precipitant and have a specific course. It is unknown which characteristics predispose sarcoidosis patients to brain or spinal cord involvement.
Treatment
Neurosarcoidosis, once confirmed, is generally treated with glucocorticoidGlucocorticoid
Glucocorticoids are a class of steroid hormones that bind to the glucocorticoid receptor , which is present in almost every vertebrate animal cell...
s such as prednisolone
Prednisolone
Prednisolone is the active metabolite of prednisone, which is also used as a drug.-Uses:Prednisolone is a corticosteroid drug with predominant glucocorticoid and low mineralocorticoid activity, making it useful for the treatment of a wide range of inflammatory and auto-immune conditions such as...
. If this is effective, the dose may gradually be reduced (although many patients need to remain on steroids long-term, frequently leading to side-effects such as diabetes
Diabetes mellitus
Diabetes mellitus, often simply referred to as diabetes, is a group of metabolic diseases in which a person has high blood sugar, either because the body does not produce enough insulin, or because cells do not respond to the insulin that is produced...
or osteoporosis
Osteoporosis
Osteoporosis is a disease of bones that leads to an increased risk of fracture. In osteoporosis the bone mineral density is reduced, bone microarchitecture is deteriorating, and the amount and variety of proteins in bone is altered...
). Methotrexate
Methotrexate
Methotrexate , abbreviated MTX and formerly known as amethopterin, is an antimetabolite and antifolate drug. It is used in treatment of cancer, autoimmune diseases, ectopic pregnancy, and for the induction of medical abortions. It acts by inhibiting the metabolism of folic acid. Methotrexate...
, hydroxychloroquine
Hydroxychloroquine
Hydroxychloroquine is an antimalarial drug, sold under the trade names Plaquenil,Axemal, Dolquine, and Quensyl, also used to reduce inflammation in the treatment of rheumatoid arthritis and lupus...
, cyclophosphamide
Cyclophosphamide
Cyclophosphamide , also known as cytophosphane, is a nitrogen mustard alkylating agent, from the oxazophorines group....
, pentoxifylline, thalidomide
Thalidomide
Thalidomide was introduced as a sedative drug in the late 1950s that was typically used to cure morning sickness. In 1961, it was withdrawn due to teratogenicity and neuropathy. There is now a growing clinical interest in thalidomide, and it is introduced as an immunomodulatory agent used...
and infliximab
Infliximab
Infliximab is a monoclonal antibody against tumour necrosis factor alpha . It is used to treat autoimmune diseases. Remicade is marketed by Janssen Biotech, Inc...
have been reported to be effective in small studies. In patients unresponsive to medical treatment, radiotherapy
Radiation therapy
Radiation therapy , radiation oncology, or radiotherapy , sometimes abbreviated to XRT or DXT, is the medical use of ionizing radiation, generally as part of cancer treatment to control malignant cells.Radiation therapy is commonly applied to the cancerous tumor because of its ability to control...
may be required. If the granulomatous tissue causes obstruction or mass effect, neurosurgical
Neurosurgery
Neurosurgery is the medical specialty concerned with the prevention, diagnosis, treatment, and rehabilitation of disorders which affect any portion of the nervous system including the brain, spine, spinal cord, peripheral nerves, and extra-cranial cerebrovascular system.-In the United States:In...
intervention is sometimes necessary. Seizures can be prevented with anticonvulsant
Anticonvulsant
The anticonvulsants are a diverse group of pharmaceuticals used in the treatment of epileptic seizures. Anticonvulsants are also increasingly being used in the treatment of bipolar disorder, since many seem to act as mood stabilizers, and in the treatment of neuropathic pain. The goal of an...
s, and psychiatric phenomena may be treated with medication usually employed in these situations.
Prognosis
Of the phenomena occurring in neurosarcoid, only facial nerveFacial nerve
The facial nerve is the seventh of twelve paired cranial nerves. It emerges from the brainstem between the pons and the medulla, and controls the muscles of facial expression, and functions in the conveyance of taste sensations from the anterior two-thirds of the tongue and oral cavity...
involvement is known to have a good prognosis and good response to treatment. Long-term treatment is usually necessary for all other phenomena.
Epidemiology
Sarcoidosis has a prevalence of 40 per 100,000. Given that less than 10% of these will have neurological involvement, and possibly later on in their disease course, neurosarcoidosis has a prevalence of less than 4 per 100,000.Notable cases
The American television personality and actress Karen DuffyKaren Duffy
Karen Duffy is an American model, television personality, and actress.-Early life:Duffy was born in New York City, the daughter of Carol, a homemaker, and Phil Duffy, a developer. She attended Park Ridge High School in Park Ridge, New Jersey, graduating in 1979...
wrote "Model Patient: My Life As an Incurable Wise-Ass" on her experiences with neurosarcoidosis.