The clinical picture of multiple sclerosis (MS) is very diverse, and there is not a single specific sign characteristic of this nosological entity, which explains the high frequency diagnostic errors. It has been established that even today, 5–10% of patients who are diagnosed with multiple sclerosis actually do not have this disease.
The most difficult thing is to establish a diagnosis at the onset of multiple sclerosis. The true onset of the disease often escapes the researcher’s field of vision, which is facilitated by the significant period of time between the clinical debut of the pathological process and its further course. Important have anamnestic data, which almost always contain an indication of the polysymptomatic nature of the disease, instability of symptoms, as well as a progressive or remitting course. It is especially important to identify the most initial, although very distant, symptoms of the disease. You should always keep in mind the possibility of misinterpretation of previous exacerbations (when collecting an anamnesis) - the presence of unilateral visual loss, Bell's palsy, trigeminal neuralgia, episodic systemic vertigo or “carpal tunnel syndrome” with sensory disturbances that do not correspond to the area of innervation of the median nerve.
The period during which patients consider themselves healthy, forgetting about the episode, can be several years. Thus, the very initial signs of the disease are often not recorded, and sometimes long-term remission makes it necessary to consider initial symptoms, which occurred many years ago, as having nothing to do with the underlying disease. Often, patients see a doctor after a second and subsequent exacerbations, usually manifested by a large number of symptoms that are more persistent than during the first attack. The first manifestations of the disease are often monosymptomatic, unstable, distant from the second exacerbation by a longer remission and are often not taken into account.
Clinical syndromes at the onset of multiple sclerosis
Theoretically, at the onset of multiple sclerosis, the development of almost any neurological symptoms is possible. However, certain areas of the central nervous system are more often affected in multiple sclerosis than others (see figure). For example, despite the relatively small amount of myelin in the optic nerves, its damage in the form of optic (retrobulbar) neuritis at the onset of the disease is observed in 15–20% of cases. To others often first Clinical manifestations of multiple sclerosis include transverse (usually incomplete) myelopathy syndrome (10–15%), ocular movement disorders, more often in the form of incomplete internuclear ophthalmoplegia (7–10%), symptoms of damage to the pyramidal tract at different levels (10%), disorders of deep and superficial sensitivity (33%), as well as dysfunction of the cerebellum and its pathways.
Retrobulbar (optic) neuritis(RBN) is manifested by dimness or blurred vision, pain when moving the eyeballs, and sometimes photophobia. Characterized by one-sidedness of the lesion, acute or subacute development, as well as reversibility of vision loss. Objectively, a decrease in visual acuity, an afferent pupillary defect, color desaturation (especially for red), and a central scotoma are detected. Low-contrast vision testing is a very sensitive method for detecting subtle lesions, which detects abnormalities even in completely normal visual acuity; V acute stage with sometimes developing papillitis, disc edema is detected in the fundus optic nerve, but with “pure” retrobulbar neuritis there are changes in acute period absent (nerve disc pallor usually develops later). Not typical for optic neuritis in multiple sclerosis include following symptoms: complete absence pain, complete loss of vision, hyperacute onset (typical of vascular etiology of neuropathy), bilateral involvement (typical of neuromyelitis optica, Leber's neuropathy), presence of fundus neuroretinitis, retinal hemorrhages, presence of fever or poor clinical recovery for one month or more after onset of symptoms.
Myelitis(incomplete transverse myelitis)
Myelitis usually incomplete transverse (impairment of not all three main functional tracts of the spinal cord - sensory, motor and regulating pelvic functions). Typical tingling sensations in the chest or abdomen reflect damage to the posterior columns and are often combined with a horizontal level of sensory disturbances. Symptoms atypical for myelitis in multiple sclerosis include hyperacute onset, the presence of longitudinal or complete transverse myelitis, severe radicular pain, and the development of spinal shock.
Stem syndrome
Stem syndromes usually presenting with incomplete internuclear ophthalmoplegia, but facial myokymia or weakness, systemic vertigo, facial sensory disturbances (may also reflect lesions in the upper cervical spinal cord or subcortically), and other syndromes are also possible.
Movement disorders
Movement disorders presented by pyramidal paresis, often unilateral and often affecting the lower extremities, may be associated with spasticity, stiffness, spasms, cramps and gait disturbance ( indicated symptoms sometimes develops in the absence of formal paresis).
Sensory impairments
Sensory impairments in the onset, for the most part, reflect foci in the posterior columns, and not in spinothalamic tracts, and a decrease in vibration sensitivity usually develops in the early stages, and always before the muscular-articular sense is impaired; sensory disturbances can be negative or positive - tingling, burning, itching, paresthesia, hyperpathia, allodynia, dysesthesia, sometimes difficult to describe (for example, a feeling of swelling of a limb, or a feeling that the skin is surrounded by fabric of clothing.
Cerebellar disorders
Cerebellar disorders in multiple sclerosis, they manifest themselves as systemic dizziness, instability (the latter, however, may reflect a disorder of deep sensitivity, vestibular system, spasticity or general weakness), clumsiness, loss of balance, and tremor. Objectively, scanned speech, recoil phenomenon, limb or gait ataxia, dysmetria and intention tremor are detected; Romberg's symptom is often reported, but usually postural disturbances are present with both open and closed eyes [Khabirov F.A., Averyanova L.A., Babicheva N.N., Granatov E.V., Khaibullin T.I., 2015].
Other symptoms
Multiple sclerosis, especially in its debut, is characterized by paroxysmal syndromes. Of the latter, tonic convulsions and paroxysmal ataxia and dysarthria are well characterized, in both cases the attacks are very short - from 10 s to 2 minutes, with a frequency of up to 10-40 per day, provoked by movements of hyperventilation; tonic spasms of spinal origin (flexion of the hand and arm) are often preceded by sensory disturbances (fever, pain) in the opposite limb; if the spasm also affects the face, then there are usually no sensory disturbances, and the focus is located in the trunk; the same applies to very short-term episodes of dysarthria and ataxia. Isolated cases of these syndromes have been described with damage to the central nervous system in SLE, but in general they are so specific for multiple sclerosis that they are considered almost pathognomonic. Other paroxysmal symptoms are less specific - glossopharyngeal neuralgia, paroxysmal itching, sudden loss of tone, kinesiogenic athetosis, hiccups, segmental myoclonus; paroxysmal also includes Lhermitte's phenomenon and trigeminal neuralgia; the latter develops in multiple sclerosis at a younger age and is often bilateral, but in general, unlike many others paroxysmal symptoms, multiple sclerosis accounts for a very small proportion of cases trigeminal neuralgia observed in routine practice. In addition to non-epileptic symptoms, true symptoms have also been described at the onset of multiple sclerosis. epileptic seizures, as a rule, within the framework of the encephalopathy syndrome with ADEM-like debut of multiple sclerosis.
According to our own data, the most common syndromes at the onset of multiple sclerosis (Figure) from a topical point of view were optic neuritis (16%) and myelopathy syndrome (20%), less common were brainstem disorders and cerebellar disorders (13 and 7%, respectively). Hemispheric sensory and motor disorders were detected in 11 and 8% of patients, and various options polyfocal debut - in 14%. We observed other variants of the onset of the disease in less than 6% of cases (mainly paroxysmal non-pileptic symptoms, epileptic seizures and encephalopathy syndrome as part of the ADEM-like onset of multiple sclerosis) [Khabirov F.A., Khaibullin T.I., Granatov E. V., Averyanova L.A., Babicheva N.N., Shakirzyanova S.R., 2015].
Drawing. The structures of the central nervous system most often affected in the onset of multiple sclerosis. Polyfocal onset variants account for approximately 14% of cases (analysis conducted on more than 800 newly identified cases of multiple sclerosis from 2010 to 2016).
Clinical syndromes in the advanced stage of multiple sclerosis
As at the onset of the disease, characteristic feature multiple sclerosis - the variety of its clinical manifestations. The disease is characterized by the formation of scattered foci of inflammation in the central nervous system, therefore it usually manifests itself with a set of symptoms associated with damage to various conduction systems.
Multiple sclerosis is characterized by a syndrome of “clinical dissociation” (“splitting”), reflecting a discrepancy between the symptoms of damage to one or more functional systems. For example, with central paresis with increased proprioreflexes and the presence of pathological pyramidal signs, instead of the expected spasticity, hypotension is detected. Another symptom typical of multiple sclerosis is the “hot bath” phenomenon (Uchthoff phenomenon), characterized by a temporary increase or appearance of symptoms as the temperature rises environment(hot bath, sauna, eating hot food, hyperinsolation) or an increase in the patient’s body temperature ( physical exercise, fever).
A qualitative assessment of neurological disorders in multiple sclerosis in accordance with international standards is carried out using the expanded disability scale (EDSS), which includes a systematic assessment of the neurological status according to Kurtzke’s 7 functional systems, as well as the patient’s ability to walk and self-care (see figure).
Drawing. A sample interface of an online EDSS calculator in Russian, which allows you to automatically calculate the EDSS score (screenshot from the website http://edss.ru).
As an expert tool and reference, the app is useful for neurologists who specialize in the diagnosis and treatment of multiple sclerosis and other demyelinating diseases and who use the EDSS on a daily basis. To expand the range of users, the program is available in 3 languages (English, Russian, German), and the interface is equally easy to use both on the screen of computers and smartphones. The EDSS calculator received a Certificate of state registration of the computer program No. 2016610500 dated January 13, 2016.
According to the pathogenesis of multiple sclerosis, the detailed clinical picture is dominated by polymorphic symptoms of damage to the central nervous system due to inflammatory and neurodegenerative damage to the pathways, especially with a developed fast-conducting myelin sheath: optic tracts, pyramidal tracts, cerebellar tracts, posterior longitudinal fasciculus, associative fibers of the cerebral hemispheres, posterior columns of the spinal cord brain, etc. Thus, in the neurological status, various combinations of asymmetric damage to the optic nerves (optic neuritis with possible subsequent partial atrophy), dysfunction oculomotor nerves(various types of strabismus, double vision, pathological reflex ocular movements in the form of nystagmus), pseudobulbar syndrome, central paresis and paralysis with spasticity, cerebellar symptoms (unsteadiness in a standing position and when walking, trembling in the limbs, slowness and scantiness of speech, decreased muscle tone ), various variants of tremulous hyperkinesis (tremor of the head, torso, limbs), sensory disturbances, dysfunction of the pelvic organs (urinary retention, urgency, constipation, incontinence), cognitive-emotional symptom complex (disorders abstract thinking, attention, increased mood, decreased criticism and self-criticism).
Cranial nerve damage
Optic neuritis often develops as the only or one of the manifestations of the next exacerbation of multiple sclerosis and is typically manifested by a unilateral decrease in visual acuity. Vision is usually partially or completely restored in varying periods - from several days to several months, but with frequent repeated neuritis it eventually develops partial atrophy optic nerves with more or less pronounced permanent visual defect (which, however, usually does not reach complete blindness)
From others cranial nerves The oculomotor muscles are most often affected. In addition to the direct damage by the demyelinating process to the intrastem areas of the nerves themselves, oculomotor disorders are often caused by damage to the posterior longitudinal fasciculus in the brain stem with the development of unilateral or bilateral internuclear ophthalmoplegia (diplopia in lateral gaze, while the inability to adduct the eyeball on the side of the lesion is observed, and horizontal nystagmus in the abducted eye). A very common symptom of multiple sclerosis is nystagmus, which can be presented in almost all variants depending on the location of the demyelination focus. For example, horizontal nystagmus, often with a rotatory component, is associated with damage to the brain stem, monocular - with involvement of the cerebellum in the process, and vertical - with damage to the oral parts of the brain stem. In the presence of nystagmus, patients often complain of blurred vision or the illusion of shaking objects (oscillopsia).
Symptoms from the V and VII pairs of cranial nerves associated with damage to the fibers that form them in the brain stem are also common. Thus, damage to the intrastem portion facial nerve manifests itself peripheral paresis facial muscles, which in some cases is part of the alternating hemiplegic syndrome. Characteristic of damage to the facial nerve in multiple sclerosis is the absence of signs of severe damage, instability of symptoms, and frequent combination with damage to other CNs. If irritation of the facial nerve fibers predominates, facial myokymia or facial hemispasm may occur. Defeat trigeminal nerve may manifest itself as neuralgia or impaired sensitivity on the face and paresis of the masticatory muscles.
Damage to the connections of the vestibular nuclei with other brainstem structures and the cerebellum is manifested by systemic dizziness, accompanied by nausea and vomiting; with simultaneous damage to the fibers belonging to the auditory portion of the VIII pair of the CN, tinnitus and/or hearing loss are possible ( latest symptoms are not common manifestations of multiple sclerosis).
Damage to the intra-trunk portions of the bulbar group nerves leads to the development of paralysis of the muscles of the soft palate, pharynx, larynx and tongue, which is manifested by dysarthria, dysphagia and dysphonia, which, however, are more often a consequence of supranuclear lesions, i.e. occur as part of pseudobulbar palsy, accompanied by violent laughter or crying.
Pyramid syndrome (pdefense of the pyramidal tracts)
Symptoms of damage to the pyramidal tract are the most common manifestation of multiple sclerosis and the main cause of disability in patients. Depending on the location of the lesion, patients may have central mono-, hemi-, tri- and tetraparesis, but lower paraparesis is most characteristic of MS. Paresis is usually accompanied by spasticity, increased proprioflexes, foot clonus and kneecaps, pathological stop marks(usually of the extensor type) and a decrease in skin reflexes, primarily abdominal ones. However, a combination is often observed central paresis with severe muscle hypotonia (due to damage to the cerebellum and/or deep sensory conductors) or with dystonia, in such cases proprioreflexes may be reduced or even absent.
Damage to sensory pathways
Sensory disturbances are observed in more than 80% of patients with multiple sclerosis. Most frequent symptoms that patients with multiple sclerosis present during examination are a feeling of numbness, burning, and a sensation of “crawling goosebumps.” These disorders are often unstable in nature and are often accompanied by painful sensations. Sensitivity disorders can be conductive or, less commonly, segmental. Mosaic sensitivity disorders are often observed. For multiple sclerosis, disturbances in deep sensitivity, in particular vibration, and muscle-articular sense, are typical, which is accompanied by the development of sensitive ataxia and sensitive paresis. When localizing foci of demyelination in spinal cord, especially within the posterior columns, Lhermitte’s symptom is possible - the occurrence, when tilting the head, of a paroxysmal sensation of electric current passing along the spine, sometimes radiating to the limbs.
Cerebellar disorders
Cerebellar disorders in multiple sclerosis can be represented by static and dynamic ataxia, dys- and hypermetry, asynergia, misses in coordination tests, scanned speech and megalography, decreased muscle tone, and ataxic gait. Intention tremor is often observed; in case of damage to the fibers connecting the dentate and red nuclei, Holmes tremor develops (a resting tremor, which intensifies in postural conditions and when attempting purposeful movements is transformed into large-scale involuntary movements that can spread to the head and torso. With damage to the cerebellar vermis, in addition to severe static ataxia, axial tremor of the head and/or trunk (titubation) is possible [Averyanova L.A., 2014].
Pelvic disorders
In the vast majority of patients with multiple sclerosis, especially with damage to the spinal cord, at a certain stage of the disease, dysfunction of the pelvic organs occurs. As a result, the synchronous functioning of the detrusor and sphincters is disrupted Bladder: hyper- or areflexia of the detrusor, detrusor-sphincter dyssynergia.
Symptoms of detrusor hyperreflexia include urinary frequency, urgency, and urinary incontinence. Detrusor areflexia - lack of urge to urinate, bladder fullness and urinary incontinence, difficulty urinating with a sluggish stream, feeling of incomplete emptying of the bladder. Detrusor-sphincter dyssynergia is characterized by incomplete emptying of the bladder with residual urine (the possibility of developing inflammatory complications), intermittent urine stream, urinary retention, accompanied by pain in the lower abdomen and perineum.
Dysfunction of the rectum is observed somewhat less frequently than pathology of urination. They are usually represented by constipation, more or less persistent, less often by an imperative urge to empty the bowel and fecal incontinence (when foci of demyelination are localized in the lumbosacral part of the spinal cord).
Disorders of the pelvic organs in men are usually combined with sexual dysfunction(impaired erection and ejaculation).
Cognitive and psychoemotional disorders
Disorders of mental and intellectual-mnestic functions as a consequence of multiple sclerosis itself or as psychological reaction the disease is often noted. They can be represented by emotional and affective disorders: depression, euphoria, neurosis-like states, and less commonly, psychosis. In some patients with multiple sclerosis, panic attacks. In milder variants of the course of the disease, mood lability, accentuation of innate personality characteristics, apathetic or anxiety states. Along with this, cognitive disorders may develop: impairments in memory, attention, abstract thinking, decreased speed of thinking, and speed of information assessment. As the disease progresses, mild or even moderate dementia may develop.
The syndrome is very characteristic of multiple sclerosis chronic fatigue- rapid physical fatigue with the need for frequent rest, emotional exhaustion, inability to wait long, limited motivation, drowsiness. A feature of this syndrome in multiple sclerosis is that the fatigue of patients is not adequate to physical or any other stress.
It is customary to distinguish four main types of MS.
Relapsing-remitting type of course
Relapsing-remitting multiple sclerosis characterized by the presence of clearly identifiable exacerbations with full restoration or with consequences and residual deficiency, periods between exacerbations are characterized by the absence of disease progression. This is the most common option multiple sclerosis, it accounts for 80 to 90% of all cases of the disease.
Secondary progressiveflow type
Secondary progressive multiple sclerosis characterized by the onset of progression after an initial relapsing-remitting course, with or without occasional exacerbations, minor remissions or plateau periods. The period from the onset of the disease to the onset of the progression stage varies and can average from 9 to 20 years or more.
Primary progressiveflow type
Primary progressive multiple sclerosis Characterized by progression from the onset of the disease, occasional periods of plateau or temporary minor improvements are possible. This rarer form accounts for up to 10% of all cases of the disease.
Progressive-recurrent type of course
Progressive-relapsing multiple sclerosis characterized by progression from the onset of the disease, with clear acute exacerbations, with or without full recovery, periods between exacerbations characterized by continued progression. This course is observed in a small proportion of patients with primary progressive disease.
In this case, an exacerbation of multiple sclerosis means the development of new or intensification of existing neurological symptoms, typical of acute inflammatory demyelinating damage to the central nervous system, lasting at least 24 hours, in the absence of fever or infectious process. Symptoms of exacerbation of multiple sclerosis can be either constant or paroxysmal (many episodes of paroxysmal disorders over at least 24 hours). Criteria for exacerbation of multiple sclerosis on the EDSS usually include a 1-point increase in at least 2 functional systems, or a 2-point increase in 1 functional system, or an increase in the EDSS score of at least 0.5 points. Two exacerbations of multiple sclerosis are considered separate if the time interval between the completion of the first and the development of the second exacerbation is at least 30 days. Disease progression is usually understood as a gradual increase in the degree of neurological disorders over 1 year or more.
Along with the listed flow variants recognized by most researchers, several additional ones are sometimes identified. For example, a benign course of multiple sclerosis with the development of minimal neurological symptoms over 10 years or more, a transient-progressive course (figure).
Drawing. Types of multiple sclerosis (MS). “Classical”: RR MS - relapsing-remitting course of multiple sclerosis; SPT MS is a secondary progressive course of multiple sclerosis; PPT MS is a primary progressive course of multiple sclerosis; PRT MS is a progressive-relapsing course of multiple sclerosis. Additional: DT MS - benign course of multiple sclerosis; TPT MS is a transient-progressive course of multiple sclerosis. Adapted from.
IN last years due to the need to more adequately reflect the modern understanding of the pathogenesis of multiple sclerosis, as well as with the aim of widespread dissemination of the term CIS and the need to take into account not only clinical, but also MRI activity of the disease, classic types the flows were revised in 2013. The definition of new flow phenotypes and their relationship with traditional ones is presented in the figure.
Drawing. New definitions of the types of multiple sclerosis. The division of the type of course into relapsing-remitting and progressive remains. The definitions of relapse and progression have not changed, however, the CIS phenotype and the descriptor of “activity” have been additionally introduced, which means the presence of either clinical exacerbations or contrast-enhancing, new or clearly enlarged T2 lesions on MRI, which is performed at least once a year. (obviously, active CIS turns into a relapsing-remitting MS phenotype). Adapted from Lublin F.D., Reingold S.C., Cohen J.A. et al., 2014.
Temporary stages of development
Widespread introduction of the term " clinically isolated multiple sclerosis syndrome"(KIS RS), and then the term " Radiologically isolated multiple sclerosis syndrome"(RIS MS) served as the basis for developing the concept of the temporal stages of development of multiple sclerosis. CIS is understood as the first episode of neurological disorders caused by inflammatory demyelinating lesions of the central nervous system, which, however, does not meet the formal diagnostic criteria for relapsing-remitting multiple sclerosis, usually due to the lack of a criterion for dissemination over time. Naturally, it is extremely important to carry out a thorough differential diagnosis and exclusion of other causes of such CNS damage. CIS can be mono- or multifocal, mono- or polysymptomatic. The most common monofocal variants of CIS are optic neuritis, incomplete transverse myelopathy, various brain stem syndromes, and hemispheric focal lesions. To date, there is not one reliable way, which could help determine whether (and when) CIS may progress to multiple sclerosis, although many different biomarkers and prognostic factors have been proposed.
As for the term “radiologically isolated syndrome” (RIS), it refers to changes that are accidentally detected on MRI, typical of multiple sclerosis, but in the absence of any clinical manifestations. To establish that a subject has an RIS, the following criteria must be met.
- A. Characteristic focal changes in the white matter of the brain according to MRI:
- ovoid-shaped, well-demarcated, homogeneous lesions involving corpus callosum or without it;
- the T2 size of hyperintense lesions is more than 3 mm and they meet the Barkov criteria (at least 3 out of 4) in terms of dissemination in space;
- white matter abnormalities do not follow the vascular pattern;
- B. There is no history of relapsing-remitting clinical symptoms neurological dysfunction;
- B. MRI abnormalities are not associated with clinically obvious impairment in social, occupational, or general functioning;
- D. MRI abnormalities are not directly related to exposure to substances (drugs, household toxins) or medical conditions;
- E. The MRI phenotype is not consistent with leukoaraiosis or widespread white matter abnormalities without involvement of the corpus callosum;
- E. Cannot be explained by other pathological processes.
The risk of transformation of RIS into CIS is not precisely known, but it is increased in the presence of spinal lesions. Thus, de facto RIS is a subclinical form of multiple sclerosis, based on this, the temporal stages of the disease can be represented as the following sequence: RIS → CIS → relapsing-remitting multiple sclerosis → secondary progressive multiple sclerosis.
Specific phenotypes of multiple sclerosis
There are several variants of multiple sclerosis, which differ from ordinary cases either in the course of the disease or in MRI (or pathomorphological picture).
Marburg disease
Marburg disease- a malignant variant of multiple sclerosis. It is characterized by an acute onset with predominant damage to the brain stem, rapid progression of the disease, and absence of remissions. Irreversible neurological disorders intensify very quickly, and after a short period of time the patient already experiences difficulties associated with movement and self-care (score of 6 points or more on the EDSS scale 3 years or earlier from the onset of the disease). Thus, the disease is characterized by an acute onset, severe course with the rapid onset of severe functional impairment, up to fatal outcome. MRI reveals multiple foci of demyelination of various sizes, including large ones, with overlapping areas of perifocal edema. The lesions are characterized by contrast enhancement and their localization in the brain stem.
Balo concentric sclerosis
Balo concentric sclerosis- a relatively rare, rapidly progressive variant of multiple sclerosis in young people, in which there is the formation of large foci of demyelination in the white matter of the hemispheres, sometimes involving the gray matter. The lesions consist of alternating areas of complete and partial demyelination, located concentrically or chaotically, which creates a typical pathomorphological picture, in most cases visualized by MRI (plaques are represented by alternating concentric areas). In some cases, the disease may have a relatively benign course, especially with timely pulse therapy with glucocorticoids.
Pseudotumorous multiple sclerosis characterized clinical picture subacutely developing space-occupying process, usually of cerebral localization; noted in patients with definite multiple sclerosis. Sometimes such a course is possible at the onset of the demyelinating process. In some cases, pseudotumor syndrome may recur. A number of features (for example, the nature of the accumulation of contrast in the form of an open ring) make it possible to differentiate this option from a tumor-like lesion of the central nervous system, however, in many cases it is necessary to conduct PET, special MRI methods, or study of a biopsy specimen.
Currently, the concepts of radiologically isolated syndrome [RIS] and clinically isolated syndrome [CIS] have been introduced into clinical practice (you can read about RIS).
The improvement of existing and introduction of new neuroimaging methods, as well as the development of new diagnostic criteria for multiple sclerosis (MS) have made it possible to sufficiently early detection. The clinical manifestation of MS does not always coincide with the actual time of its onset. In approximately 90% of MS cases, the first episode of demyelination occurs in the form of a so-called “clinically isolated syndrome”, when there are no signs of “dissemination in time”, and signs of “dissemination in space” are either present or absent.
Clinically isolated syndrome ( CIS) [currently defined as] is a monophasic (i.e., for the first time with a relatively rapid onset) symptomatology, or more precisely, an individual clinical episode that is caused by a presumably inflammatory demyelinating disease. "CIS" has a synonym - "first demyelinating episode" (or "first episode of demyelination").
Remember! CIS is characterized by the formation of neurological symptoms within 2 - 3 weeks without any apparent reason and in the absence of fever. Characteristic feature CIS is a regression of symptoms.
The most common manifestations of CIS are unilateral retrobulbar neuritis, trigeminal neuralgia, transverse myelitis, Lhermitte's sign, bilateral internuclear ophthalmoplegia, paroxysmal dysarthria/ataxia, paroxysmal tonic spasms, or sensory disturbances.
(! ) We should not forget that CIS is not always the first manifestation of MS, but can be a manifestation of diseases such as a tumor of the brain or spinal cord, cervical spondylosis, cerebral vasculitis, sarcoidosis, mitochondrial encephalopathy, etc.
The symptoms detected during CIS serve as objective [clinical] signs of one or more foci of demyelination in the brain or spinal cord (in 50-70% of cases of CIS, multiple subclinical foci of demyelination are detected already at the first MRI); sometimes with monosymptomatic CIS, it is also possible to identify clinically “silent” foci of demyelination (i.e., additionally, signs of multiple lesions of the central nervous system are detected, which confirms dissemination in space). Thus, in CIS, patients may present with different combinations of neurological symptoms and MRI findings; Moreover, despite the fact that it is possible to simultaneously detect multiple clinical/paraclinical manifestations [CIS], however, dissemination over time should not be obvious. In this regard, in modern classification The following types (variants) of CIS are distinguished:
type 1
- clinically monofocal; at least 1 asymptomatic MRI lesion;
type 2
- clinically multifocal; at least 1 asymptomatic MRI lesion;
type 3
- clinically monofocal; MRI may be without pathology; no asymptomatic MRI lesions;
type 4
-clinically multifocal; MRI may be without pathology; no asymptomatic MRI lesions;
type 5
- There are no clinical findings suggestive of demyelinating disease, but there are suggestive MRI findings.
Thus, The criterion for “CIS” is not the semiotic-topic (syndromic) isolation of clinical neurological symptoms, but its (i.e. symptoms) “temporary” A I am limited” - monophasic (i.e., absence of signs of dissemination over time); CIS can be monofocal or multifocal, but always without signs of dissemination over time, i.e. always limited in time - monophasic.
It is difficult to predict whether MS will develop after the first episode, but the currently used McDonald criteria (due to the widespread use of MRI and its increasing role in the diagnosis of MS) allow, in a certain percentage of cases of CIS, to establish a diagnosis of definite MS before the development of a second clinical attack. C. Dalton et al. (2003) found that the use of the McDonald criteria allows more than twice as often to diagnose MS within the first year after detection of CIS, without waiting for a second episode of demyelination. Identification of 9 (nine) or more lesions on a tomogram that do not accumulate contrast agent is an important prognostic sign of MS.
Note! Increasingly in routine clinical practice in patients undergoing magnetic resonance imaging (MRI) for examination for indications such as traumatic brain injury or migraine, white matter pathology in the central nervous system(CNS). These changes can be either nonspecific (described by radiologists as “unidentified light objects”) or highly characteristic of demyelinating pathology, taking into account their morphology and localization in the central nervous system. It was proposed to highlight the latter in “ radiologically isolated syndrome" (RIS), which precedes clinically isolated syndrome (CIS) and is the first clinical manifestation of multiple sclerosis.
note .
Pierre Duquette and Jolly Proulx-Therrien, Multiple Sclerosis Clinic, Hospital Center de l'Université de Montréal, Canada
A clinically isolated syndrome can be defined as a manifestation of the onset (harbinger) of MS.
The clinical diagnosis of MS requires the presence of two occurrences separated in time and involvement of different areas of the central nervous system. With the advent of MRI of the brain and spinal cord, it is now possible to identify individuals at risk of developing multiple sclerosis, as it shows a clinically isolated syndrome. Multiple studies have better defined the risk of “conversion” from clinically isolated syndrome to multiple sclerosis—evidence that conversion of disease-modifying treatment to the clinically isolated syndrome stage delays both conversion of MS and the onset of the progressive stage.
Natural science
The clinical presentation of initial signs is highly variable. However, typically people with clinically isolated syndrome are young Caucasian adults ( average age begins to appear by age 30). In 46% of cases, the clinically isolated syndrome (damage) resides in the spinal cord, more often presenting with sensory than motor symptoms. The optic nerve is the second most common site, as 21% of people with clinically isolated syndrome have acute optic neuritis. Multifocal signs (involving more than one site in the central nervous system) are encountered in 23% of cases. Others will have damage in the brain stem, or in the cerebral hemispheres. After several weeks, these symptoms disappear partially or completely.
The natural long-term history of people with clinically isolated syndrome is now better known through observation of groups with clinically isolated syndrome followed for up to 20 years. Optic neuritis, as recently reported by the Optic Neuritis Study Group, is associated with an overall 50% risk of developing MS 15 years after onset. On the other hand, cerebellar or multifocal symptoms and poor recovery are usually associated with a poor prognosis.
Optic neuritis may cause blurry vision
Temporary blindness and pain behind the eye
Diagnosis
Since a clinically isolated syndrome is a possible prelude to multiple sclerosis, it is of utmost importance to rule out other conditions. This is done through history, clinical examination, and blood work (to rule out systemic and other autoimmune diseases). The two main tests are MRI of the brain and spinal cord, and cerebral fluid examination. MRI shows infammatory lesions with features consistent with demyelization in 90% of cases. These lesions establish a clinical suspicion of multiple sclerosis and have an impact on the risk of conversion to RRMS and, subsequently, to SPMS. One study of 107 people concluded that 80% of people with clinically isolated syndrome with abnormal MRI, and 20% with normal MRI, will develop clinically defined multiple sclerosis after age 20. A higher number of damages carries more high risk MS transformation and an earlier stage of secondary progression.
Approximately 70 percent of people with clinically isolated syndrome will eventually develop MS regardless of the presence of lesions on MRI. In some countries, lumbar punctures are performed less frequently in establishing the diagnosis of clinically definite multiple sclerosis and rarely for clinically isolated syndrome.
Treatment
Steroids, usually high-dose IV methylprednisolone, are used to treat acute exacerbations that cause new symptoms or worsen existing symptoms. Identifying those at high risk of clinically isolated syndrome and introducing early disease-modifying therapies is of primary importance.
Multiple clinical trials with interferon beta have established its effectiveness in reducing recurrence rates and delaying disease progression. Interferon beta has anti-infammatory properties and can improve the integrity of the blood-brain barrier.
These placebo trials (subjects in the study who are not on active treatment) found that the longer treatment is delayed, the greater the risk of progression of disability. Three clinical trials have shown that interferon beta can reduce the risk of a second episode by 50% over two years. In fact, 40% of people with clinically isolated syndrome will develop clinically definite multiple sclerosis within two years. If therapy is started two years after clinically isolated syndrome, the risk for CDMS is higher when compared with patients who received early treatment(49% of those with delayed treatment versus 36% of those treated early, before five years. Identifying those who are at high risk of clinically isolated syndrome and introducing early disease-modifying therapy is of primary importance.
Similar results, in people with clinically isolated syndrome and MS, have been achieved glatiramer acetate- a synthetic form of myelin protein that causes a suppressive response against lymphocytes reactive to antigens in the central nervous system.
Natalizumab, a humanized monoclonal antibody that prevents the infiltration of activated lymphocytes across the blood-brain barrier in the central nervous system, has not been tried in humans with clinically isolated syndrome.
In conclusion: clinically isolated syndrome is now recognized as the initial manifestation of multiple sclerosis with clinically isolated syndrome, those who have infammatory lesions on MRI of the brain or spinal cord, are at high risk of early conversion to clinically identified MS, possibly also to an earlier stage of secondary progression. Studying these people with interferon beta or with glatiramer acetate slows down these events.
Modern drugs can change the course of this serious disease
It took Michelle Maglioni three years to clarify the diagnosis of multiple sclerosis.
Her first exacerbation occurred in 1988, when she experienced a frightening attack of numbness in the lower part of the body, starting from the lower back. Then she decided that she had suffered a displacement of a vertebra or a pinched nerve from some sudden movement. She was referred to a neurologist, who confirmed that she had a herniated disc and prescribed physical therapy. After a few months, the numbness went away. Maglioni was then 30 years old, she was actively working in one of the New York public organizations. She tried to put what had happened out of her mind.
But the disease took revenge for the lack of attention, making itself felt again when Michelle was visiting friends in Europe. “This time they refused right hand And left leg", she recalls. Returning home, she turned to another neurologist, who officially diagnosed her with multiple sclerosis in June 2001. A month later, she began regularly taking a new disease-modifying drug with proven ability to slow the progression of multiple sclerosis.
Lucky with the diagnosis
Surprisingly, Maglioni considers herself lucky. “During the time that elapsed from the diagnosis to the start of treatment, I began to lose peripheral vision, she says. – For me it was even more terrible than everything physical symptoms that I had." After two months of treatment, peripheral vision was restored, and some other symptoms disappeared. There were still some symptoms of the disease - for example, a tingling sensation in her left palm - but Michelle knew that things could have been much worse if her diagnosis had remained unclear for a long time.
Until relatively recently, it would not have mattered much whether Maglioni was diagnosed at an early or late stage of the disease. “We had no treatments, and all she could theoretically expect was some insurance and labor benefits"recalls Dr. Patricia Coyle, professor of neurology at the State University of New York at Stony Brook, director of the Center complex treatment multiple sclerosis in Stony Brook.
Today everything has changed. Experts are now unanimous that the use of basic drugs for the treatment of multiple sclerosis (including Avonex, Betaseron, Copaxone, Novantrone and Rebif) provides the best chance of delaying the development of the disease, provided that treatment is started early. Recent scientific research suggests that the best protective effect would be achieved if these drugs were given immediately after the first clinical episode (clinically isolated syndrome), although a formal diagnosis of multiple sclerosis cannot be made until the patient has suffered at least two attacks of illness.
What is “clinically isolated syndrome”?
Clinically isolated syndrome (CIS) can be considered the “first attack” of multiple sclerosis, explains Dr. Coyle. This is a single clinical exacerbation, indicating the presence of demyelinating changes (destruction of the protective substance covering the nerve endings in the brain and spinal cord). For example, unilateral optic neuritis or numbness on one side of the body may be considered CIS. Clinically isolated syndrome is usually not accompanied by any other clinical signs or symptoms, and (as was the case with Maglioni), one can come up with many other explanations for the sudden numbness of one hand or deterioration in vision. However, according to Dr. Coyle, if your doctor has ruled out other possible reasons, and an MRI study showed the presence of characteristic changes, an episode of CIS should be a reason to discuss the issue with a doctor possible destination basic therapy against multiple sclerosis.
Benefits of early treatment for multiple sclerosis
According to Dr. Coyle, research suggests that young people who have only a clinically isolated syndrome, but have certain changes on MRI of the brain, have a very high risk of developing multiple sclerosis. “There have been three large, independent, phase 3 trials, and all three have shown better prognosis for patients in this group with disease-modifying MS drugs compared with placebo,” she says. These studies, which examined the effects of the drugs Avonex, Betaseron and Rebif, found that the use of any of them in patients who had suffered a single clinical episode helped to delay the onset of overt multiple sclerosis. How long this protective effect may last remains to be determined through ongoing scientific research.
When a person with multiple sclerosis develops a “clinically isolated syndrome” (an example is Michelle Maglioni's lower body numbness in 2001), it means that the disease has already been developing in the brain for some time. Dr. John Richert, vice president of research and programs at the Multiple Sclerosis Society of America, compares the process to the motion of a locomotive rolling downhill. “Once started, the autoimmune reaction develops further like a train passing over a mountain range. It's much easier to brake it at the very beginning of the descent than later when it gains uncontrollable acceleration,” he says.
Slow down multiple sclerosis
Despite the fact that treatment was not started after the first attack in 2001, Maglioni believes that starting basic therapy for multiple sclerosis, even at the stage at which it was done, made it possible to “slow down” the “locomotive” of her disease that had begun to accelerate - according to at least for a while. “Since starting to take the drug, I have not had a single obvious exacerbation. And there have been no new plaques on MRI for the last two years,” she says. “This is the best I can hope for: the medicine works as it should - it slows down the development of the disease and prevents exacerbations from developing.”
But multiple sclerosis failed to “slow down” Maglioni’s vital activity. Today she is vice president of communications for the New York chapter of the Multiple Sclerosis Society of America. She actively participates in fundraising events, organizing teams to march against multiple sclerosis and even swimming a three-mile distance across the Hudson as part of a campaign to raise money for research and other programs on multiple sclerosis.
“I remember what I felt when I first heard my diagnosis - I was literally crushed by it. But if ever being diagnosed with multiple sclerosis could be considered lucky, it is only in our time, when so many basic drugs have been created that change the course of the disease. And new drugs are on the way, and there is much more knowledge about this disease now than just 10 years ago,” she says. “Doctors can already do a lot to keep our disease under control, but we who live with this disease must act together with them.”
