Neurosarcoidosis is a manifestation of systemic sarcoidosis, which is a progressive lesion of the nervous system. The disease is characterized by the formation of non-caseous granulomas in the tissue of the brain and spinal cord, cranial and peripheral nerves. The clinical picture depends on the localization of granulomas, is represented by pyramidal and extrapyramidal disorders, meningeal symptoms. Possible mental disorders, hydrocephalus. During the diagnosis, CT and MRI of the organs of the central nervous system, histological examination of the intra-thoracic lymph nodes are performed. Glucocorticosteroids are used for treatment.
ICD 10
D86.8 Sarcoidosis of other specified and combined localizations
General information
Sarcoidosis is an inflammatory disease characterized by the formation of granulomas in various organs (more often – in the lungs, lymph nodes, liver and spleen). The occurrence of neurosarcoidosis indicates an extremely severe and neglected systemic pathological process, in some situations – already non-curable. The nervous system is involved in 10-25% of cases, but clinical symptoms are observed only in 5-10% of patients. Almost all patients, along with neurological manifestations, have signs of damage to other organs and systems. Isolated neurosarcoidosis occurs only in 11-15% of cases.
Causes
To date, the exact etiological factor of this pathology has not been established. More frequent morbidity among close relatives can be considered as proof of hereditary predisposition. Sarcoidosis is regarded as a multifactorial nosology. There are several known triggers that trigger a hyperergic cellular immune response. The most common of them are infectious agents.
Antigenic stimuli (herpes simplex virus, Epstein-Barr), bacteria (chlamydia, borrelia) can lead to the development of neurosarcoidosis. The environmental factor capable of provoking the formation of sarcoidal granulomas is the constant exposure to metal dust (aluminum, cobalt). Regarding smoking, the data are contradictory. On the one hand, smoking reduces the frequency of acute forms of the disease, on the other hand, smoking patients have a higher percentage of resistance to standard therapy.
Pathogenesis
Nonimmune granuloma is considered to be the main morphological substrate of neurosarcoidosis. The formation of granulomas in all organs occurs according to the same scheme. Under the influence of an unknown etiological agent, T-lymphocytes are activated that secrete cytokines (interleukin-2, gamma interferon), which have chemotactic activity in relation to monocytes, which subsequently transform into macrophages, and then into epithelioid cells.
They merge into giant Pirogov-Langhans cells surrounded by fibroblasts and plasma cells. The final stage is fibrosis and hyalinosis. Constantly forming new granulomas disrupt the functioning of organs. In addition to other chemicals (tumor necrosis factor, etc.), activated macrophages secrete the enzyme 1-alpha-hydroxylase, which converts vitamin D into the active form. This explains hypercalcemia in neurosarcoidosis.
Classification
Depending on the localization of sarcoid granulomas , the following variants of neurosarcoidosis are distinguished:
- The brain.
- Spinal cord.
- Peripheral nervous system.
Neurosarcoidosis of the brain, in turn, is divided into lesions of the cerebellum, meninges, pseudotumorosis (volumetric process) and multi-focal forms.
Neurosarcoidosis symptoms
The clinical course of the disease is extremely variable – it can be slow or fast, with remissions or steadily progressing. Long before the formation of a detailed picture, nonspecific symptoms are observed: general weakness, prolonged temperature rise to subfebrile figures. Then signs characteristic of all types of sarcoidosis are added: arthralgia, myalgia, skin rashes in the form of nodular erythema.
Manifestations of brain damage
The most common symptom of neurosarcoidosis is a headache of various localization, gradually increasing and taking on a permanent character. With the involvement of the meninges, nausea, vomiting, rigidity of the occipital muscles worries. Coordination of movements is disrupted, there is a feeling of stiffness in the arms and legs, the gait changes. Possible tremor of the hands as with Parkinsonism. Typically, the sudden development of hemiparesis and hemiplegia with increased tendon and the appearance of pathological reflexes.
Cognitive functions suffer – memory deteriorates, concentration of attention decreases. With the progression of the process, the handwriting changes, the understanding of speech and spatial thinking is disrupted. More than half of the patients have mental disorders. Many complain of insomnia or nightmarish dreams. Mood variability is characteristic – from euphoria to a tendency to depression. Visual and auditory hallucinations are very rare.
Manifestations of spinal cord injury
For this type of neurosarcoidosis, the slow development of radiculomyelopathy in the form of radicular pain and hyperalgesia is typical, changing to hypesthesia until complete loss of sensitivity. There are symptoms such as weakness in the limbs, trophic changes in the skin of the hands and feet, a decrease in tendon reflexes (sluggish paresis or paralysis). In severe cases, pelvic disorders (involuntary urination and defecation) are added.
Signs of peripheral nerve sarcoidosis
Cranial nerves are often involved, especially the facial one, which is manifested by Bell’s palsy (numbness of the skin and paralysis of the facial muscles), and bilateral. Sometimes the pharyngeal nerve is affected, which is why the act of swallowing is disrupted. Polyneuropathies are often found – muscle tone and sensitivity in the extremities decrease, paresthesia (tingling, burning, crawling goosebumps) are noted.
Pain in the feet and shins is characteristic, which increases when walking. Polyneuropathies with neurosarcoidosis are accompanied by vegetative disorders – dryness, cold, cyanosis of the skin of the feet. There are symptoms of dysfunction of the cardiovascular system (orthostatic hypotension) and the gastrointestinal tract due to paresis of the stomach (pain, heaviness in the epigastric region, belching rotten).
Complications
Neurosarcoidosis has a large number of complications, including fatal ones. The causes of death are edema and insertion of the brain in hydrocephalus, paresis of the diaphragm, thromboembolism due to prolonged immobilization caused by tetra- or paraplegia. Excessive irritation of cortical structures with granulomas can provoke an epileptic seizure.
With neurosarcoidosis, the hypothalamic-pituitary zone is often involved in the pathological process with the development of neuroendocrine disorders – hyperprolactinemia, diabetes insipidus (in 20% of patients), hypothalamic hypothyroidism. Due to hypercalcemia, calcium ions are deposited in the renal tubules and vessels, which can lead to chronic kidney disease.
Diagnostics
Due to the systemic nature of the process, patients with neurosarcoidosis require a multidisciplinary approach, joint supervision by a neurologist and a pulmonologist is necessary. Since the symptoms are quite nonspecific, it is very important to identify in the anamnesis an indication of previously diagnosed lung sarcoidosis. Additional examination aimed at clarifying the diagnosis includes:
- Laboratory tests. In the general blood test, markers of inflammation are noted – leukocytosis, an increase in ESR. The biochemical analysis of blood reveals a large concentration of C-reactive protein, gamma globulins, ionized calcium. The detection of high numbers of angiotensin-converting enzyme is considered specific. In the cerebrospinal fluid obtained by lumbar puncture, lymphocytic pleocytosis is found, a violation of the CD4: CD8 ratio.
- MRI of the spinal cord and brain. On MRI with contrast, thickening of the meninges, signs of hydrocephalus (asymmetry of the ventricles, expansion of the basal cisterns), polymorphic granulomas with clear contours, perifocal edema and good accumulation of contrast are determined.
- CT of the lungs. Since neurosarcoidosis almost always develops a second time against the background of pulmonary sarcoidosis, it is advisable to perform chest CT. The technique confirms the presence of intra-thoracic lymphadenopathy, diffuse interstitial infiltrates.
- Histological examination. A verification method for the diagnosis of neurosarcoidosis. Epithelioid cell granulomas, inflammatory infiltration, axonal degeneration and demyelination are detected in the biopsy of spinal or brain tissue, sensory nerve.
Differential diagnosis of neurosarcoidosis is carried out with brain tumors, stroke, Parkinson’s disease. When the meninges are affected, the disease is distinguished from tuberculosis or viral meningitis. It is necessary to exclude demyelinating pathologies (Guillain-Barre syndrome, multiple sclerosis), polyneuropathies of other etiology.
Treatment
Conservative therapy
All patients are subject to mandatory hospitalization with the neurological department. The basis of treatment is glucocorticosteroid drugs (prednisolone, methylprednisolone). They suppress the activity of the inflammatory process and prevent the transition of granulomatous inflammation into fibrosis (its occurrence is due to the irreversibility of neurological disorders). Therefore, the use of glucocorticoids is most effective at an early stage of the disease.
Against the background of treatment with hormonal agents, a rapid regression of symptoms and normalization of the tomographic picture occurs, however, long-term medication is necessary to maintain remission, since their early withdrawal inevitably leads to relapse and deterioration of the patient’s condition. An exception is isolated facial neuropathy, for which a short 2-week course is sufficient for treatment.
In the acute course of neurosarcoidosis, treatment should begin with pulse therapy, followed by a transition to daily oral medication. In case of resistance to GCS or their intolerance, immunosuppressants are prescribed – methotrexate (necessarily with folic acid), azathioprine, cyclophosphamide or synthetic antimalarial drugs (chloroquine, hydroxychloroquine).
In some cases, radiation therapy of the cranial region is effective. With the involvement of the hypothalamic-pituitary zone, endocrinological disorders are irreversible, therefore, their development requires lifelong hormone replacement therapy (with hypothyroidism – levothyroxine, with diabetes insipidus – vasopressin analogues).
Surgical treatment
Surgical removal of granulomas is resorted to only in extreme cases – with the ineffectiveness of all methods of conservative therapy, the steady growth of formations and the development of a gross neurological deficit that threatens the patient’s life. At the same time, it is taken into account that surgical intervention in itself can worsen the condition of patients with neurosarcoidosis. In case of hydrocephalus, an emergency bypass operation is indicated.
Prognosis and prevention
Neurosarcoidosis is a serious disease with an unpredictable course. A favorable prognosis is possible only in patients with polyneuropathies, isolated cranial neuropathies or aseptic meningitis. The most unfavorable outcome is observed in patients with multiple lesions of GM and hydrocephalus. The main cause of death is cerebral edema.
Prevention consists in timely diagnosis and competent treatment of pulmonary sarcoidosis. Since neurosarcoidosis involves long-term use of GCS, regular monitoring of blood pressure, blood glucose concentration and bone mineral density is necessary for timely detection of adverse side effects.