Radiologically isolated syndrome (MRI criteria and patient management). Clinically isolated Kiss syndrome


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 (precursor) of MS.

The clinical diagnosis of MS requires two repetitions, 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 people at risk for developing multiple sclerosis, as it shows a clinically isolated syndrome. Multiple studies have made it possible to better define the risk of "transformation" from a clinically isolated syndrome to multiple sclerosis - evidence that the transformation of a disease-modifying treatment into a clinically isolated syndrome stage delays both the transformation of MS and the onset of a progressive stage.

natural science

The clinical presentation of initial symptoms is highly variable. However, typically people with a clinically isolated syndrome are young Caucasian adults (median age of onset is 30 years of age). In 46% of cases, a clinically isolated syndrome (lesion) sits in the spinal cord, presenting more often with sensory than with motor symptoms. The optic nerve is the second most common site, as 21% of people with clinically isolated syndrome have acute optic neuritis. Multifocal findings (involving more than one site in the central nervous system) are encountered in 23% of cases. Others will have damage in the brainstem, or in the cerebral hemispheres. After a few 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 up to 20 years. Optic neuritis, as recently 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 poor prognosis.

Optic neuritis can 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 examinations of cerebral fluid. MRI shows infammatory lesions with features consistent with demilitarization in 90% of cases. These lesions establish 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 lesions carries a higher risk of MS transformation and an earlier stage of secondary progression.

Approximately 70 percent of people with a clinically isolated syndrome will eventually develop MS, regardless of the presence of lesions on MRI. In some countries, lumbar punctures are less common in establishing a diagnosis of clinically defined multiple sclerosis and rare for a clinically isolated syndrome.

Treatment

Steroids, usually high IV doses of methylprednisolone, are used to treat acute exacerbations that cause new symptoms or worsen existing symptoms. The identification of those at high risk for a clinically isolated syndrome and the introduction of early disease-modifying therapy is of major importance.

Multiple clinical trials with interferon beta have established their effectiveness in reducing relapse rates and delaying disease progression. Interferon beta has anti-infammatory properties and is able to improve the integrity of the blood-brain barrier.

The placebo of these trials (subjects in the study who are not on active treatment) found that the longer treatment is delayed, the higher the risk of disability progression. 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 a clinically isolated syndrome will develop clinically defined multiple sclerosis within two years. If therapy is started two years after a clinically isolated syndrome, the risk for CDMS is higher when compared with patients who received early treatment (49% of those with delayed treatment vs. 36% of those treated early, up to five years. Identification of those who has a high risk of a clinically isolated syndrome and the introduction of early disease-modifying therapy is of major importance.

Similar results, in people with clinically isolated syndrome and MS, have been achieved. glatiramer acetate- a synthetic form of myelin protein that causes an overwhelming response against lymphocytes reactive to antigens in the central nervous system.

Natalizumab, a humanized monoclonal antibody that prevents activated lymphocytes from infiltrating the blood-brain barrier into the central nervous system, has not been tried in people with a clinically isolated syndrome.

In conclusion: clinically isolated syndrome is now recognized as the initial manifestation of multiple sclerosis with clinically isolated syndrome who has infammatory lesions on MRI of the brain or spinal cord, at high risk of early transformation 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.

The clinical picture of multiple sclerosis (MS) is very diverse, while there is not a single specific symptom characteristic of this nosological unit, which explains the high frequency of diagnostic errors. It has been established that even at present, 5-10% of patients who are diagnosed with multiple sclerosis do not actually have this disease.

The most difficult is the diagnosis at the debut of multiple sclerosis. The true onset of the disease often escapes the researcher's field of vision, which is facilitated by a significant period of time between the clinical debut of the pathological process and the further course. Anamnestic data are important, which almost always contain an indication of the polysymptomatic nature of the disease, the instability of symptoms, as well as a progressive or relapsing course. It is especially important to identify the most initial, albeit very distant symptoms of the disease. You should always keep in mind the possibility of misinterpretation of previous exacerbations (when collecting anamnesis) - the presence of unilateral loss of vision, Bell's palsy, trigeminal neuralgia, episodic systemic vertigo or "carpal tunnel syndrome" with sensory disturbances that do not correspond to the region of innervation of the median nerve.

The period during which patients consider themselves healthy, forgetting about the episode that has occurred, can be several years. Thus, the very initial signs of the disease are often not fixed, and sometimes a long remission makes one regard the initial symptoms that took place many years ago as having nothing to do with the underlying disease. Often, patients come to the doctor after the second and subsequent exacerbations, as a rule, 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, remote from the second exacerbation by a longer remission and are often not taken into account.

Clinical syndromes at the onset of multiple sclerosis

Theoretically, in the debut of multiple sclerosis, the development of almost any neurological symptomatology is possible. However, certain areas of the CNS are more commonly 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. Other frequent first clinical manifestations of multiple sclerosis include transverse (usually incomplete) myelopathy syndrome (10–15%), oculomotor 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 dysfunctions of the cerebellum and its pathways.

Retrobulbar (optical) neuritis(RBN) is manifested by dull or blurred vision, pain when moving the eyeballs, and sometimes photophobia. One-sidedness of the lesion, acute or subacute development, as well as reversibility of visual impairment are characteristic. Objectively, a decrease in visual acuity, an afferent pupillary defect, color desaturation (especially in red), and a central scotoma are detected. For the detection of a mild lesion, a very sensitive method is the study of low-contrast vision, which reveals anomalies even with completely normal visual acuity; in the acute stage, with sometimes developing papillitis in the fundus, edema of the optic nerve head is detected, but with “pure” retrobulbar neuritis, there are no changes in the acute period (paleness of the nerve disk usually develops later). Symptoms that are not typical for optic neuritis in multiple sclerosis include the following symptoms: complete absence of pain, complete loss of vision, superacute onset (typical for vascular etiology of neuropathy), bilateral involvement (typical for optomyelitis, Leber's neuropathy), the presence of neuroretinitis in the fundus, retinal hemorrhages , the presence of fever, or poor clinical recovery for one month or more after the onset of symptoms.

Myelitis(incomplete transverse myelitis)

Myelitis usually incomplete transverse (violation of not all three main functional tracts of the spinal cord - sensory, motor and regulating pelvic functions). Girdle tingling sensations in the chest or abdomen are typical, reflecting damage to the posterior pillars and often associated with a horizontal level of sensory disturbances. Symptoms atypical for myelitis in multiple sclerosis include a hyperacute onset, the presence of longitudinal or complete transverse myelitis, severe radicular pain, and the development of spinal shock.

stem syndrome

stem syndromes usually presents with incomplete internuclear ophthalmoplegia, but facial myokymia or weakness, systemic dizziness, sensory disturbances on the face (may also reflect lesions in the upper cervical spinal cord or subcortically) and other syndromes are also possible.

Movement disorders

Movement disorders represented by pyramidal paresis, more often unilateral and more often affecting the lower extremities, may be associated with spasticity, stiffness, spasms, cramps and gait disturbance (these symptoms sometimes develop in the absence of formal paresis).

Sensory disturbances

Sensory disturbances in the debut, for the most part, they reflect foci in the posterior columns, and not in the spinothalamic pathways, and a decrease in vibration sensitivity usually develops in the early stages, and always before the violation of the muscular-articular feeling; sensory disturbances can be negative or positive - tingling, burning, itching, paresthesias, hyperpathy, allodynia, dysesthesias, sometimes difficult to describe (for example, a feeling of swelling of a limb, or a feeling that the skin is surrounded by clothing fabric.

Cerebellar disorders

Cerebellar disorders with multiple sclerosis, they are manifested by systemic dizziness, instability (the latter, however, may reflect a disorder of deep sensitivity, the vestibular system, spasticity or general weakness), clumsiness, loss of balance, tremor. Scanned speech, rebound phenomenon, ataxia of limbs or gait, dysmetria and intentional tremor are detected objectively; Romberg's symptom is often reported, but usually postural disturbances are present both with open and closed eyes [Khabirov F.A., Averyanova L.A., Babicheva N.N., Granatov E.V., Khaibullin T.I., 2015].

Other symptoms

For multiple sclerosis, especially in the debut, paroxysmal syndromes are characteristic. Of the latter, tonic convulsions and paroxysmal ataxia and dysarthria are well characterized, in both cases the attacks are very short - from 10 seconds to 2 minutes, with a frequency of up to 10–40 per day, provoked by hyperventilation movements; tonic convulsions of spinal origin (flexion of the hand and arm) are often preceded by sensory disturbances (heat, pain) in the opposite limb; if the spasm also captures the face, then sensory disturbances are usually absent, and the focus is located in the trunk; the same applies to very brief episodes of dysarthria and ataxia. Isolated cases of these syndromes are described with CNS lesions 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, Lermitte's phenomenon and trigeminal neuralgia also belong to paroxysmal ones; the latter develops in multiple sclerosis at a younger age and is often bilateral, but in general, unlike many other paroxysmal symptoms, multiple sclerosis causes a very small proportion of cases of trigeminal neuralgia observed in routine practice. In addition to non-epileptic ones, true epileptic seizures are also described in the debut of multiple sclerosis, as a rule, within the framework of the encephalopathy syndrome in ADEM-like debut of multiple sclerosis.

According to our own data, the most common syndromes in the onset of multiple sclerosis (figure) from a topical point of view were optic neuritis (16%) and myelopathy syndrome (20%), stem disorders and cerebellar disorders were less common (13 and 7%, respectively). Hemispheric sensory and motor disorders were detected in 11% and 8% of patients, and various variants of 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].

Picture. The structures of the central nervous system that are most often affected in the debut of multiple sclerosis. Polyfocal onset variants account for approximately 14% of cases (the analysis was conducted on more than 800 newly diagnosed cases of multiple sclerosis from 2010 to 2016).

Clinical syndromes in the advanced stage of multiple sclerosis

As in the debut of the disease, a characteristic feature of multiple sclerosis is 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 as a set of symptoms associated with damage to various conduction systems.

Multiple sclerosis is characterized by the syndrome of "clinical dissociation" ("splitting"), which reflects the discrepancy between the symptoms of damage to one or more functional systems. For example, with central paresis with an increase in 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 (Uhthoff phenomenon), characterized by a temporary increase or the appearance of symptoms when the ambient temperature rises (hot bath, bath, hot food, hyperinsolation) or the patient’s body temperature rises (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 7 Kurtzke functional systems, as well as the patient's ability to walk and self-care (see figure).

Picture. A sample interface of an online EDSS calculator in Russian that allows you to automatically calculate the EDSS score (screenshot from the website http://edss.ru).

As an expert tool and reference, the application is useful for neurologists who specialize in the diagnosis and treatment of multiple sclerosis and other demyelinating diseases and use the EDSS on a daily basis. To expand the circle 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 the Certificate of state registration of the computer program No. 2016610500 dated January 13, 2016.

According to the pathogenesis of multiple sclerosis, the clinical picture is dominated by polymorphic symptoms of CNS damage due to inflammatory and neurodegenerative lesions of the pathways, especially with a developed fast-conducting myelin sheath: optic pathways, pyramidal tracts, cerebellar tracts, posterior longitudinal bundle, associative fibers of the cerebral hemispheres, posterior columns of the spinal cord. brain, etc. Thus, in the neurological status, various combinations of asymmetric lesions of the optic nerves (optic neuritis with possible subsequent partial atrophy), dysfunction of the oculomotor nerves (various types of concordance, double vision, pathological reflex ocular movements in the form of nystagmus), pseudobulbar syndrome, central paresis and paralysis with spasticity, cerebellar symptoms (unsteadiness in standing position and when walking, trembling in the limbs, slowness and scantiness of speech, decreased muscle tone), various types of tremulous hyperkinesis (trembling of the head, trunk, limbs), sensory disturbances, dysfunctions of the pelvic organs ( urinary retention, imperative urge, constipation, incontinence), a cognitive-emotional symptom complex (disorders of abstract thinking, attention, increased mood, reduced criticism and self-criticism).

Damage to cranial nerves

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 various periods - from several days to several months, but with frequent repeated neuritis, partial atrophy of the optic nerves eventually develops with a more or less pronounced permanent visual defect (which, however, usually does not reach complete blindness)

Of the other cranial nerves, the oculomotor nerves are most commonly affected. In addition to direct damage to the intrastem sections of the nerves themselves by the demyelinating process, oculomotor disorders are often caused by damage to the posterior longitudinal bundle in the brain stem with the development of unilateral or bilateral internuclear ophthalmoplegia (diplopia in lateral gaze, while observing the impossibility of bringing the eyeball to the side of the focus, and horizontal nystagmus in the retracted eye). A very common symptom of multiple sclerosis is nystagmus, which can be represented by almost all variants, depending on the localization of the focus of demyelination. For example, horizontal nystagmus, often with a rotator component, is associated with lesions of the brainstem, monocular - with involvement of the cerebellum, and vertical - with damage to the oral parts of the brainstem. In the presence of nystagmus, patients often complain of blurred vision or the illusion of objects trembling (oscillopsia).

There are also frequent symptoms from the V and VII pairs of cranial nerves associated with damage to the fibers that form them in the brain stem. Thus, damage to the intratruncal portion of the facial nerve is manifested by peripheral paresis of the facial muscles, which in some cases is part of the alternating hemiplegic syndrome. Characteristic for the defeat of the facial nerve in multiple sclerosis is the absence of signs of a gross lesion, the instability of symptoms, as well as the frequent combination with lesions of other CNs. With the predominance of irritation of the fibers of the facial nerve, the appearance of facial myokymia or facial hemispasm is possible. The defeat of the trigeminal nerve can be manifested by neuralgia or impaired sensitivity on the face and paresis of the masticatory muscles.

Damage to the connections of the vestibular nuclei with other stem 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 CNs, tinnitus and / or hearing loss are possible (the latter symptoms do not belong to frequent manifestations of multiple sclerosis).

The defeat of the intrastem portions of the nerves of the bulbar group 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 the result of supranuclear lesions, i.e. occur within the framework of pseudobulbar palsy, accompanied by violent laughter or crying.

Pyramidal syndrome (ndestruction of the pyramidal tracts)

Symptoms of lesions of 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 focus, patients may have central mono-, hemi-, tri-, and tetraparesis, but lower paraparesis is most characteristic of MS. Paresis, as a rule, is accompanied by spasticity, increased proprioreflexes, clonus of the feet and kneecaps, pathological foot signs (often extensor type) and a decrease in skin reflexes, primarily abdominal ones. However, a combination of central paresis with severe muscular hypotension (due to damage to the cerebellum and / or conductors of deep sensitivity) or with dystonia is often observed, in such cases proprioreflexes may be reduced or even absent.

Sensory pathway damage

Sensitivity disorders are observed in more than 80% of patients with multiple sclerosis. The most common symptoms that patients with multiple sclerosis present during the examination are a feeling of numbness, burning, a feeling of "crawling". These disorders are often unstable, often accompanied by pain. Sensory disturbances may be conductive or, less commonly, segmental. Mosaic sensitivity disorders are often observed. For multiple sclerosis, violations of deep sensitivity, in particular vibration, and muscular-articular feeling are typical, which is accompanied by the development of sensitive ataxia and sensitive paresis. With the localization of foci of demyelination in the spinal cord, especially within the posterior columns, Lermitte's symptom is possible - when the head is tilted, a paroxysmal sensation of the passage of electric current along the spine, sometimes radiating to the limbs, occurs.

Cerebellar disorders

Cerebellar disorders in multiple sclerosis can be represented by static and dynamic ataxia, dys- and hypermetry, asynergy, misses in coordination tests, scanned speech and megalography, decreased muscle tone, and atactic gait. Intentional tremor is often observed; in case of damage to the fibers that connect the dentate and red nuclei, Holmes's tremor develops (rest tremor, which increases in postural conditions and, when purposeful movements are attempted, it transforms into large-scale involuntary movements that can spread to the head and trunk. In case of 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 lesions of the spinal cord, at a certain stage of the disease, disorders of the functions of the pelvic organs occur. As a result, the synchronous work of the detrusor and sphincters of the bladder is disrupted: hyper- or areflexia of the detrusor, detrusor-sphincter dyssynergia.

Symptoms of detrusor hyperreflexia are frequent urination, urgency, and urinary incontinence. Detrusor areflexia - lack of urge to urinate, overflow of the bladder and urinary incontinence, difficulty urinating with a sluggish stream, a feeling of incomplete emptying of the bladder. Detrusor-sphincter dyssynergy is characterized by incomplete emptying of the bladder with residual urine (the possibility of developing inflammatory complications), intermittency of the urine stream, urinary retention, accompanied by pain in the lower abdomen and perineum.

Violations of the function of the rectum are observed somewhat less frequently than the pathology of urination. They are usually represented by constipation, more or less persistent, less often by imperative urge to empty the intestines and fecal incontinence (with localization of demyelination foci in the lumbosacral part of the spinal cord).

Dysfunction of the pelvic organs in men is usually combined with sexual dysfunction (erection and ejaculation disorders).

Cognitive and psycho-emotional disorders

Disorders of mental and intellectual-mnestic functions as a consequence of multiple sclerosis itself or as a psychological reaction to the disease are often noted. They can be represented by emotional-affective disorders: depression, euphoria, neurosis-like states, less often - psychoses. Some patients with multiple sclerosis experience panic attacks. With milder variants of the course of the disease, mood lability, accentuation of innate personality traits, apathetic or anxious states are noted. Along with this, cognitive disorders can develop: impaired memory, attention, abstract thinking, reduced speed of thinking, speed of information evaluation. As the disease progresses, mild or even moderate dementia may develop.

For multiple sclerosis, chronic fatigue syndrome is very characteristic - 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 load.

It is customary to distinguish four main types of MS flow.

Relapsing-remitting type of course

Relapsing-remitting multiple sclerosis characterized by the presence of clearly defined exacerbations with complete recovery or with consequences and residual deficits, the periods between exacerbations are characterized by the absence of disease progression. It is the most common variant of multiple sclerosis, accounting for 80 to 90% of all cases of the disease.

secondary progressiveflow type

Secondary progressive multiple sclerosis characterized by the onset after an initial relapsing-remitting course by progression, accompanied or not accompanied by 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 plateaus or temporary minor improvements are possible. This rarer form accounts for up to 10% of all cases.

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 complete recovery, the periods between exacerbations are characterized by ongoing progression. This course is noted in a small proportion of patients with primary progressive disease.

At the same time, an exacerbation of multiple sclerosis means the development of a new or an increase in already existing neurological symptoms, typical of an acute inflammatory demyelinating lesion of the central nervous system, lasting at least 24 hours, in the absence of fever or an infectious process. Symptoms of an exacerbation of multiple sclerosis can be both permanent and paroxysmal (many episodes of paroxysmal disorders within at least 24 hours). Criteria for exacerbation of multiple sclerosis on the EDSS scale usually include an increase of 1 point in at least 2 functional systems or 2 points 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. The progression of the disease is usually understood as a gradual increase in the degree of neurological disorders for 1 year or more.

Along with the listed variants of the flow recognized by the majority of researchers, several additional ones are sometimes distinguished. For example, a benign course of multiple sclerosis with the development of minimal neurological symptoms for 10 years or more, a transient progressive course (figure).

Picture. Types of course of multiple sclerosis (MS). "Classic": RR MS - relapsing-remitting course of multiple sclerosis; VPT MS - secondary progressive course of multiple sclerosis; PPT MS - 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 recent 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 wide dissemination of the term CIS and the need to take into account not only clinical, but also MRI disease activity, the classical types of the course were revised in 2013. Definition of new phenotypes currents and their relationship with traditional ones is shown in the figure.


Picture. New definitions of the types of course of multiple sclerosis. The division of the type of flow into relapsing-remitting and progressive is preserved. The definitions of recurrence and progression have not changed, however, the phenotype of CIS and the descriptor of “activity” have been added, which means the presence of either clinical exacerbations or contrasted, new or clearly increased T2 lesions on MRI, which is performed at least once a year. (it is obvious that active CIS turns into the phenotype of the relapsing-remitting course of MS). Adapted from Lublin F.D., Reingold S.C., Cohen J.A. et al., 2014.

Time stages of development

The widespread use of the term " clinically isolated multiple sclerosis syndrome"(KIS RS), and then the term" Radiologically isolated multiple sclerosis syndrome» (RIS RS) served as the basis for the development of the concept of the time stages of the development of multiple sclerosis. CIS is understood as the first episode of neurological disorders caused by an inflammatory demyelinating lesion of the CNS, 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 conduct a thorough differential diagnosis and exclude other causes of such damage to the central nervous system. CIS can be mono- or multifocal, mono- or polysymptomatic. The most common monofocal variants of CIS are optic neuritis, incomplete transverse myelopathy, various stem syndromes, hemispheric focal lesions. To date, there is no reliable way to determine if (and when) CIS can progress to multiple sclerosis, although many different biomarkers and prognostic factors have been proposed.

As for the term "radiologically isolated syndrome" (RIS), then it means changes that are accidentally detected during MRI, typical of multiple sclerosis, but in the absence of any clinical manifestations. To state that a subject has RIS, the following criteria must be met.

  • A. Characteristic focal changes in the white matter of the brain according to MRI:
  • ovoid, well-circumscribed, homogeneous lesions with or without involvement of the corpus callosum;
  • the size of T2 hyperintense foci 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 match the vascular pattern;
  • B. There is no history of remitting clinical symptoms of neurological dysfunction;
  • C. MRI abnormalities are not associated with clinically obvious impairments in social, occupational, or general function;
  • D. Anomalies on MRI are not directly related to exposure to substances (drugs, household toxins) or medical conditions;
  • E. MRI phenotype does not correspond to 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 exactly 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 time 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 the usual cases either by the features of the course, or by MRI (or pathomorphological picture).

Marburg disease

Marburg disease- a malignant variant of multiple sclerosis. It is characterized by an acute onset with a predominant lesion of the brain stem, rapid progression of the disease, and the absence of remissions. Irreversible neurological disorders increase very quickly, and after a short time the patient already experiences difficulties associated with movement and self-care (score of 6 points or more on the EDSS scale after 3 years and earlier from the onset of the disease). Thus, the disease is characterized by an acute onset, a severe course with a rapid onset of pronounced functional disorders, up to a lethal outcome. MRI reveals multiple foci of demyelination of various sizes, including large ones, with overlapping zones of perifocal edema. Characterized by contrast enhancement of foci, their localization in the brain stem.

Balo's concentric sclerosis

Balo's 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 with the involvement of the gray matter. The foci consist of alternating areas of complete and partial demyelination, located concentrically or chaotically, which creates a typical pathomorphological picture, in most cases visualized on 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 by a clinical picture of a subacutely developing volumetric process, as a rule - cerebral localization; noted in patients with significant multiple sclerosis. Sometimes such a course is also possible in the debut 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 variant from a tumor-like lesion of the central nervous system, however, in many cases, PET, special MRI methods, or a biopsy study are necessary.

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 the introduction of new methods of neuroimaging, as well as the development of new diagnostic criteria for multiple sclerosis (MS) made it possible to detect it early enough. The clinical manifestation of MS does not always coincide with the real time of its onset. In approximately 90% of cases of MS, the first episode of demyelination proceeds as a so-called "clinically isolated syndrome", when there are no signs of "dissemination in time" yet, 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) frolicking symptomatology, or rather, a frolicking single clinical episode, which is caused by a presumably inflammatory demyelinating disease. "CIS" has a synonym - "the first demyelinating episode" (or "the first episode of demyelination").

Remember! CIS is characterized by the formation of neurological symptoms within 2 to 3 weeks without any apparent cause and in the absence of fever. A characteristic feature of CIS is the regression of symptoms.

Most often, CIS is manifested by unilateral retrobulbar neuritis, trigeminal neuralgia, transverse myelitis, Lhermitte's symptom, bilateral internuclear ophthalmoplegia, paroxysmal dysarthria/ataxia, paroxysmal tonic spasms, or sensory impairment.

(! ) It should not be forgotten that CIS is not always the first manifestation of MS, but may be a manifestation of such diseases as a tumor of the brain or spinal cord, cervical spondylosis, cerebral vasculitis, sarcoidosis, mitochondrial encephalopathy, etc.

The symptoms detected in 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, clinically “silent” foci of demyelination can also be detected (i.e., signs of multiple CNS lesions are additionally detected, which confirms dissemination in space). Thus, patients with CIS may present with various combinations of neurological symptoms and MRI findings; at the same time, despite the fact that simultaneous detection of multiple clinical / paraclinical manifestations [CIS] is possible, however, dissemination over time should not be obvious. In this regard, in the modern classification of CIS, the following types (options) are distinguished:

type of 1 - clinically monofocal; at least 1 asymptomatic MRI lesion;
type of 2 - clinically multifocal; at least 1 asymptomatic MRI lesion;
type of 3 - clinically monofocal; MRI can be without pathology; no asymptomatic MRI lesions;
type of 4 - clinically multifocal; MRI can be without pathology; no asymptomatic MRI lesions;
type of 5 - no clinical features suggestive of demyelinating disease, but suggestive MRI findings.

In this way, the criterion of "CIS" is not the semiotic-topic (syndromic) isolation of clinical neurological symptoms, but its (i.e. symptoms) "temporal a I am limited” - monophasic (i.e., the absence of signs of dissemination in 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 MacDonald 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 application of the McDonald criteria allows diagnosing MS more than twice as often during the first year after the detection of CIS, without waiting for the second episode of demyelination. The detection of 9 (nine) or more lesions on the tomogram that do not accumulate a contrast agent is an important prognostic sign of MS.

Note! Increasingly, in routine clinical practice, patients undergoing magnetic resonance imaging (MRI) for examination for indications such as traumatic brain injury or migraine are additionally diagnosed with white matter pathology in the central nervous system (CNS). These changes can be either non-specific (described by radiologists as “unidentified light objects”) or highly characteristic of demyelinating pathology, taking into account their morphology and localization in the CNS. The latter were proposed to be singled out in " radiologically isolated syndrome» (RIS), preceding the clinically isolated syndrome (CIS) and being the first clinical manifestation of multiple sclerosis.

note .

Clinically isolated syndrome (CIS) is the result of a single episode of demyelination in one (monofocal episode) or several parts of the central nervous system (multifocal episode). In 85% of patients who are eventually diagnosed with multiple sclerosis, the first manifestation of symptoms of the disease or the first relapse (attack, exacerbation) is called a clinically isolated syndrome (CIS).

If, along with clinical manifestations, MRI of the brain and spinal cord reveals lesions characteristic of MS, then, in some cases, a clinically isolated syndrome can be considered as the debut of multiple sclerosis. If over time, after CIS, a clinical picture of the second episode of exacerbation of the disease develops, or new foci of demyelination are detected on subsequent MRI, then reliable multiple sclerosis is diagnosed.

However, not all patients who experience a clinically isolated syndrome develop multiple sclerosis later on. Many do not show the characteristic MRI picture of demyelination and subsequently do not develop new symptoms.

Diagnosis of clinically isolated syndrome

In diagnosing a clinically isolated syndrome, it is important to rule out other possible causes of symptoms. The medical history, neurological examination, and a range of clinical tests combine to help identify or rule out any other potential causes of the symptom(s). However, MRI is the most informative diagnostic method that allows visualizing possible foci of demyelination in the central nervous system.

The symptoms detected in CIS often indicate the localization of the focus of demyelination. Most often, foci are found in the following parts of the central nervous system:

  • spinal cord - in this case, we are talking about transverse myelitis;
  • optic nerves - in this case, we are talking about optic neuritis (retrobulbar neuritis);
  • brain stem

If the damage is clinically manifested in any one department of the CNS, then it is called "monofocal", if it occurs in several at once, then we are talking about a "multifocal" disorder.

The most common manifestations of CIS

Transverse myelitis

Transverse myelitis occurs when the myelin sheaths covering the nerve fibers of the spinal cord are destroyed.

Depending on in which part of the spinal cord the focus of demyelination is located (cervical, thoracic, lumbar, sacral), disturbances occur in the work of the corresponding organs, upper or lower extremities.

There are four main symptoms of transverse myelitis:

  • Weakness in arms and/or legs
  • Sensory disturbance
  • Bladder and colon dysfunction

Optic neuritis (retrobulbar neuritis)

Optic neuritis (retrobulbar neuritis) is caused by demyelination of the optic nerve, which transmits images from the retina to the back of the cerebral cortex. Acute attack of optic neuritis is characterized by

  • sudden loss of visual acuity,
  • pain when moving the eyeballs,
  • color vision disorder (dyschromatopsia)

Pathological processes in the brain stem

Sometimes pathological processes of demyelination affect the brainstem - part of the base of the brain, in which the nuclei of the cranial nerves and vital centers (respiratory, vasomotor and a number of others) are located. Symptoms of brainstem damage are varied and may include:

  • various oculomotor disorders, nystagmus
  • dysarthria, swallowing disorders
  • violation of statics, coordination, etc.

Treatment of clinically isolated syndrome

Depending on the nature and severity of symptoms observed in clinically isolated syndrome, corticosteroid therapy may be recommended to reduce the severity and duration of symptoms. If necessary, symptomatic therapy may be prescribed to reduce the severity or completely compensate for symptoms.

Probability of developing MS

The results of some long-term clinical studies indicate that 50% of people who have had CIS develop multiple sclerosis within five years. To date, there is no method that would allow to determine the individual risk of developing multiple sclerosis after suffering a clinically isolated syndrome.

However, researchers have attempted to identify factors that may influence the likelihood of developing MS. The presence or absence of these factors cannot determine the absolute risk of developing MS, however, in some cases, they may be useful in making decisions about further treatment.

  • Optic neuritis is associated with a lower risk of developing definite MS, and better prognostic data in the event of the disease, than other types of clinically isolated syndrome.
  • Isolated sensory symptoms, which may include numbness, tingling, or visual disturbances, are thought to be associated with a lower risk of developing MS compared with symptoms suggestive of musculoskeletal involvement. In CIS associated with movement disorders, the risk of developing MS is increased.
  • Absence of lesions on MRI is associated with a lower risk of developing MS, while scans showing a large number or volume of lesions are associated with a high risk of definitive multiple sclerosis.

Sometimes, in order to confirm or exclude the diagnosis of multiple sclerosis, a laboratory analysis of cerebrospinal fluid (CSF) is necessary - the fluid that bathes the brain and spinal cord. The presence of specific markers in CSF may indicate MS.

Criteria for the Diagnosis of Relapsing-Remitting and Progressive Multiple Sclerosis - Clinically and Radiological Isolated Syndromes

Diagnosis of Multiple Sclerosis

Diagnosis of multiple sclerosis is based on specific symptoms, findings on neurological examination, the evolution of symptoms over time, and MRI changes of the brain and spinal cord. Diagnostic criteria continue to evolve, and MRI findings now play a key role in the diagnosis of multiple sclerosis.

Some of the criteria, however, remain unshakable.
Namely - dissemination in time and space . This means that new symptoms must occur over time ( dissemination in time ) and involve numerous parts of the central nervous system ( dissemination in space ).

There are two types of multiple sclerosis: relapsing-remitting and progressive .

The first is characterized by periodic exacerbations, or relapses , which are separated in time by periods of recovery and relative well-being, or remissions . Neurological disorders acquired during the relapse period partially or completely disappear.

In primary progressive multiple sclerosis, neurological disorders develop gradually, imperceptibly, so it is difficult to say exactly when the disease began or worsened. The relapsing-remitting form of multiple sclerosis can develop into a progressive form over the years, and then multiple sclerosis is called secondary progressive.

The first episode of relapsing-remitting multiple sclerosis is called clinically isolated syndrome . A clinically isolated syndrome may be the only one in a lifetime. However, more often, over the years, the disease will manifest itself as multiple sclerosis.

Some of the classic syndromes for MS are described below, but even typical symptoms, in the absence of a sufficient set of criteria, do not mean the presence of this disease. The criteria for making a diagnosis of multiple sclerosis are described later on this page.

Typical Clinically Isolated Syndromes

Neuritis of the Optic (Optical) Nerve

Typical optic neuritis in multiple sclerosis manifests itself as some degree of loss of vision, often accompanied by pain in the eye. Pain often precedes vision loss and is provoked by eye movement. The degree of vision loss varies from a blurred image to a complete loss of light perception. Further - partial or complete restoration of vision takes several weeks. You can find a more detailed description on the page “Neuritis of the Optic Nerve”,
Optic neuritis can occur as an independent disease, and may be one of the symptoms of multiple sclerosis. In cases where there are no signs of multiple sclerosis on an MRI of the brain, the likelihood of its development over the next 15 years is about 25 percent. The presence of demyelination lesions on MRI increases this probability to 72 percent over a similar period of time.

Cerebellar Symptoms and Brain Stem Symptoms

Involvement of these structures is typical of multiple sclerosis. The classic syndromes are internuclear ophthalmoplegia , sixth nerve palsy(impossibility to take the eye to the side and, accordingly, double vision), ataxia(kind of incoordination), nystagmus(sharp involuntary eye movements), goosebumps and numbness on the face, dizziness, hearing loss. By analogy with optic neuritis, with normal MRI, the probability of multiple sclerosis in the future is about 20%, and in the case of the presence of demyelination on MRI, the probability rises to 60-90%.

Transverse Myelitis in MS

Myelitis, or inflammation of the spinal cord, is not unique to MS. This disease is described in more detail on the corresponding page. Here I will describe only the features of transverse myelitis in multiple sclerosis.
Symptoms of transverse myelitis progress over hours or days. The absence of significant weakness in the legs is quite typical, so that the symptoms may be limited to all sorts of discomfort, numbness or tingling below the level of the neck. These sensations may involve only the legs or all four limbs, including the trunk, and need not be symmetrical. In the case of involvement of the cervical spinal cord, Lermit's symptom often occurs.
Symptoms may be limited to one limb and even loss of one kind of sensation - for example, loss of sense of position in space in one hand. The reduction and even complete disappearance of neurological disorders over time, even in the absence of treatment, are quite typical.
In the absence of classically multiple sclerosis changes on MRI of the brain and / or spinal cord, the probability of developing multiple sclerosis in the future is about 20%. The presence of demyelination on MRI increases this probability to 60-90%.

Radiological Isolated Syndrome

Typical changes in multiple sclerosis on MRI of the brain and / or spinal cord, in the absence of any symptoms in the past or present, is called a radiological isolated syndrome.
In cases where a sufficient number and location of classic demyelinating changes are found on MRI, the probability of developing diffuse is from 30 to 59%.
At this stage, the criteria for the diagnosis of radiological isolated syndrome are in the process of development.

Diagnostic Criteria for Relapsing-Remitting Multiple Sclerosis

In light of the fact that the approach to the treatment of multiple sclerosis has changed over the past years, the need for early diagnosis of this disease has increased. The following description is based on McDonald's 2010 criteria.

Multiple sclerosis begins in a relapsing-remitting form in 80-85% of cases. The first symptoms occur most often between the ages of 20 and 40, and in 90% they occur between the ages of 15 and 50. In only one percent of cases, the disease can begin before 10 or after 50 years. In women, relapsing-remitting multiple sclerosis is much more common.

The disease begins with one or more of the symptoms described on the Symptoms of Multiple Sclerosis page, which last from days to weeks. Further, neurological disorders are partially or completely restored. The diagnosis of multiple sclerosis remains presumptive until a subsequent exacerbation occurs or other evidence of "dissemination over time" is found, such as on MRI.

Suppose no evidence of multiple sclerosis has been found in the past. In this case, the probability of disease in the future is somewhere around 20-25%. This is called "clinically isolated syndrome".

Followed by an MRI of the brain and spinal cord. The absence of demyelinating plaques on MRI carries the best prognosis. In cases where foci of demyelination are found on MRI, the likelihood of multiple sclerosis in the future increases to 60-90%.

Nevertheless, the criterion of dissemination in space and time remains valid. If MRI with contrast reveals recent demyelination and its location is consistent with symptoms, then the diagnosis of multiple sclerosis remains only speculative, although its likelihood in the future is very significant. Many experts, however, regard this as multiple sclerosis and believe that it is necessary to start treatment.

Either way, what follows is the wait. It is advisable to repeat the MRI after a few months, even if there are no new symptoms. New lesions of demyelination, even in the absence of symptoms, mean that it is multiple sclerosis.
The same applies to subsequent exacerbations. An exacerbation of the disease with new symptoms, even without new MRI findings, means multiple sclerosis. In both cases, the criterion of dissemination in space and time is considered to be satisfied. Similarly, when old foci of demyelination are found on MRI during the first attack of multiple sclerosis, this confirms the diagnosis of multiple sclerosis.

The progressive nature of the disease is assessed by new changes on MRI, by new symptoms, and by the level of disability accumulated over time.

What MRI Findings Are Considered Specific for Multiple Sclerosis?

The shape and location of demyelinating plaques is the most important. Typical plaques are oval in shape and are located near the ventricles of the brain (in the corpus callosum), in the immediate vicinity of the cerebral cortex (juxtacortical), in the brainstem, cerebellum, or in the spinal cord.

It is not typical for multiple sclerosis to involve the entire thickness of the spinal cord. The plaques are typically located along the periphery of the section, and along the length they occupy no more than two segments of the spinal cord. More widespread involvement of the spinal cord most often means another disease, such as neuromyelitis optic.

The presence of at least one plaque in any two of the above areas of the nervous system is considered specific for multiple sclerosis. I realize that as a non-specialist these terms are confusing, but that's exactly what the MRI report would say.

A spinal tap is no longer required to make a diagnosis of relapsing-remitting multiple sclerosis. However, in doubtful cases, this type of diagnosis remains valid. The presence of oligoclonal bands and an elevated IgG index are specific to multiple sclerosis.

Diagnostic Criteria for Primary Progressive Multiple Sclerosis

Primary progressive multiple sclerosis occurs in 10-15% of patients with multiple sclerosis. Unlike the relapsing-remitting form, its frequency does not depend on gender. The mean age of onset is 40 years (30 years for the relapsing-remitting form).

The most common first symptoms are gradually progressive gait disturbances, weakness and stiffness in the legs, imbalance and, at some stage, urinary and fecal incontinence. Sensory disturbances are uncommon. Neurological disorders usually progress slowly without remissions, although temporary partial recovery may occur in some patients.

In contrast to the relapsing-remitting form, in progressive multiple sclerosis, “degenerative” changes in the tissues of the central nervous system are the main cause of the resulting neurological disorders. There are no signs of an "inflammatory" or autoimmune nature in this form. The demyelinating process in the cerebral cortex, brain atrophy and damage to nerve fibers in the tissues of the central nervous system are much more pronounced in the progressive form of multiple sclerosis. The real mechanism for the development of this form of multiple sclerosis is not known and remains hypothetical.

In primary progressive multiple sclerosis, the spinal cord is most affected, which explains the typical symptoms in this form. Less commonly, the brain stem is involved in the disease process. Demyelination foci do not tend to show up on MRI contrast, they look pale, non-contrast, and there are usually not many of them.

McDonald criteria for the diagnosis of primary progressive multiple sclerosis:

  • At least one specific focus of demyelination is periventricular, in close proximity to the cerebral cortex (juxtacortical lesions), in the brainstem, or in the cerebellum
  • At least two lesions in the spinal cord
  • Increased IgG index or the presence of oligoclonal bands in the cerebrospinal fluid
Secondary Progressive Multiple Sclerosis

Secondary progressive multiple sclerosis develops in 25-40% of cases of the relapsing-remitting form of the disease. It develops in the later stages, about 20 years after the onset of the relapsing-remitting form of the disease.

Secondary progressive multiple sclerosis is characterized by gradually progressive disturbances in gait and balance, muscle stiffness, and urinary incontinence, regardless of disease exacerbations. Relapses may continue, but the above symptoms are observed regardless of them.

Typical symptoms, MRI, and cerebrospinal fluid examination are usually sufficient to confirm the diagnosis.
There are other diseases with similar symptoms to the progressive form of multiple sclerosis. They are not discussed in this article.

The information on the site is provided for educational purposes only. Please do not self-medicate! The final diagnosis of your health problems remains the prerogative of medical professionals. The material of the site will only help you to get acquainted with the potential ways of diagnosing and treating neurological diseases and increase the productivity of your communication with doctors. The information on the site is updated whenever possible, taking into account recent changes in the approach to the diagnosis and treatment of neurological diseases. However, the author of the articles does not guarantee that the information will be updated immediately as it becomes available. I would be grateful if you share your thoughts: [email protected]
Content copyright 2018. . All rights reserved.
By Andre Strizhak, M.D. Bayview Neurology P.C., 2626 East 14th Street, Ste 204, Brooklyn, NY 11235, USA

@ 2022 wowway.ru - Diets and nutrition. Diagnostics and analyses. Medicines. Cholesterol. Atherosclerosis