Do you know the diagnosis and treatment of clinically isolated syndrome?

Clinically isolated syndrome (CIS) refers to the first occurrence of an inflammatory demyelinating event in the central nervous system (CNS), with related symptoms and objective signs lasting at least 24 hours, and a monophasic clinical course, similar to multiple sclerosis (MS) A typical clinical episode of , but not yet diagnosed as .
CIS is a type of idiopathic inflammatory demyelinating diseases (IIDD.
For CIS, information such as clinical features, imaging and laboratory examinations of patients should be integrated to identify the risk of their progression to MS as early as possible, and then develop effective acute exacerbation treatment and possible disease-modifying treatment (DMT) programs to relieve symptoms, Shorten disease duration, control disease progression, and improve prognos.
Learn the clinical manifestations, diagnosis and differential diagnosis of CIS, assessment of the risk of transformation to multiple sclerosis, and related treatment and follow-up through the latest consensus tod.
Clinical manifestations of CIS Common clinical manifestations of CIS include vision loss, limb numbness, limb weakness, urinary and defecation disorders, e.
The clinical episodes are isolated in time (single episode), and the clinical symptoms last for more than 24 hou.
The clinical presentation depends on the anatomical site of the lesion and can be unilateral optic neuritis, focal supratentorial syndrome, focal brainstem or cerebellar syndrome, and non-transverse myelitis, which can be single or multiple appear at the same ti.
These symptoms are divided into typical and atypic.
The typical ones are highly suggestive of clinical diagnosis of MS (CDMS), while the atypical ones need to be differentiated from other demyelinating diseas.
See Table 1 for detai.
 ➤Recommendation: For clinically discovered CNS demyelination events, it is necessary to judge whether the attack is a typical CIS manifestation according to clinical characteristics, so as to help the subsequent differential diagnosis and formulate treatment strategi.
 Table 1 Diagnosis and differential diagnosis of CIS ➤Diagnostic principles The medical history, clinical symptoms and signs should be the basic bas.
First, when the patient has only subjectively changed symptoms, it is necessary to actively look for objective evidence of current or past episodes, that is, the patient reports that the affected part of the nervous system pointed to by the current or past symptoms requires a physical examination or an objective auxiliary examinati.
Evidence, including imaging, neurophysiological examinati.
Second, various auxiliary examinations should be fully combined, especially MRI imaging findings and cerebrospinal fluid oligoclonal zone (OCB) resul.
Other auxiliary examinations include neurophysiological examination, optical coherence tomography (OCT), immunological related tests ( In particular, diagnostic biomarkers for IIDDs),e.
It is worth noting that MRI is an important tool to assist in the diagnosis of C.

However, MRI should not be overly relied upon, and the characteristics of MRI lesions and their clinical relevance should be strictly explain.

Third, other possible diseases need to be ruled o.

In short, there is no unified diagnostic standard for CIS, which is prone to misdiagnos.

Because there are no specific clinical symptoms or laboratory indicators, the diagnosis of CIS should be fully integrated with clinical and subclinical eviden.

 ➤Differential diagnosis CIS diagnosis is a rigorous process of exclusion diagnosis, and it is necessary to avoid categorizing IIDDs and other non-inflammatory demyelinating diseases that cannot be "clearly explained" as CIS without adequate differential diagnos.

CIS is a clinical syndrome consisting of a single episode of CNS inflammatory demyelination even.

The clinical manifestations are diverse and atypic.

It can involve an anatomical site or a compound clinical manifestation of simultaneous involvement of multiple sit.

CIS first needs to be differentiated from other diseases with similar clinical and imaging features, see Table In addition, some clinical manifestations do not support the diagnosis of CIS, such as vertical gaze palsy, oculomotor nerve palsy, localized dystonia, torticollis, acute urinary retention, e.
 Table 2​ ➤ Recommendations: The diagnosis of CIS needs to be supported by objective evidence of anatomical site involvement and corresponding auxiliary examination evidence; a strict differential diagnosis process is required, and CIS can only be diagnosed after excluding other interpretable caus.

CIS auxiliary examination points ➤ Cerebrospinal fluid examination Routine cerebrospinal fluid examination (at least including routine, biochemical, and OCB tests) is recommend.

The 2017 revised McDonald MS diagnostic criteria use CSF OCB as surrogate evidence for temporal polymorphism, and CSF examination is strongly recommended in the following situations: (1) The clinical and MRI evidence in patients with CIS is insufficient to support the diagnosis of MS, especially when considering the initiation of treatment; (2) ) Clinical symptoms, imaging, and laboratory tests are not consistent with typical CIS; (3) CIS and MS are relatively rare in populations (eg, children, the elderly, and non-white.

The commonly used detection method for CSF OCB is isoelectric focusing electrophores.

Typical OCB positivity refers to abnormal bands that appear in cerebrospinal fluid but not in serum, suggesting abnormal synthesis of immunoglobulins in the shea.

CSF OCB test results can be divided into 5 types, of which type II and type III are positive for CSF O.

A negative OCB cannot rule out the diagnosis of MS or C.

When the patient has typical clinical manifestations of CIS, MRI imaging features, e.

, even if the OCB is negative, the diagnosis of CIS can be consider.

 ➤MRI examination: CIS lesions that are typical or have a high risk of MS transformation should be consistent with the distribution and morphological characteristics of MS lesions, namely: (1) More than 3 lateral ventricular lesio.

(2) Cortical and near-cortical lesio.

(3) Brain stem and cerebellar lesio.
(4) Short-segment non-transverse spinal cord lesions (the lesions are usually >3mm and <2 vertebral segments, <1/2 of the spinal cord area on the cross-section, and the edema is mil.

Note that the length of spinal cord lesions in Asian MS patients may be ≥2 vertebral segments, and the detection of aquaporin-4 (AQP4) antibodies can help identify NMO.

(5) Unilateral short-segment optic nerve lesions that generally do not involve the optic chiasm (increased T2WI signal, gadolinium contrast enhancement, and optic nerve thickening) are mostly round or oval in shape with clear boundari.

Special attention should be paid to the identification of other IIDDs, such as NMOSD, the spinal cord lesions are mostly transverse spinal cord lesions with more than 3 segments, and the optic nerve lesions often exceed half the length of the optic nerve or involve the optic chiasm, and are prone to lesions in the extreme posterior regi.

 ➤Blood biomarker detection Serum AQP4 antibody detection is strongly recommended for patients with suspected IIDDs to identify with NMOSD; myelin oligodendrocyte glycoprotein (MOG) antibody detection is strongly recommended to identify MOG-related diseas.

For patients with typical imaging findings or clinical symptoms suggestive of autoimmune glial fibrillary acidic protein (GFAP) astrogliosis, GFAP antibody detection can be select.

The above antibody detection methods recommend indirect immunofluorescence (CBA) based on cellular substrat.

 ➤Other examinations If there is clinical evidence that the optic nerve, brainstem, spinal cord and other corresponding anatomical parts are involved, the following examinations can be selected: ophthalmological examination (visual acuity, visual field, fundus, OCT, mainly to evaluate the patient's optic nerve damage), neurophysiological examination ( Visual evoked potentials, somatosensory evoked potentials, brainstem auditory evoked potentials, mainly to assess the patient's optic nerve, brainstem, spinal cord damage), e.

, to fully evaluate the specific site and severity of the patient's disea.

 ➤Recommendation: CSF OCB, MRI, and serum specific antibody markers have high value in the diagnosis and differential diagnosis of C.
It is recommended to complete the above examinations for all patients considered clinically as C.

 Risk factors for the outcome of CIS to CDMS Table 3 ➤ Demographic characteristics Young women (<30 years old) are at higher risk for the outcome of .

 ➤Genes and environmental factors Genes (HLA-DRB1*1501; especially in patients with abnormal baseline MRI), vitamin D deficiency (serum vitamin D level <50 nmol/L), smoking (especially in patients with abnormal baseline MRI) were considered as CIS Exact risk factors for progression to .

Infections occurring in childhood or adolescence (especially EB virus infection), areas with high incidence of MS, and sunshine hours may be risk factors for the conversion of CIS to .

It is generally believed that any single factor mentioned above is less likely to trigger MS and is often the result of a combined effe.

 ➤Clinical manifestations Current research evidence suggests that factors such as motor or multifocal symptoms, cerebellar symptoms, sphincter dysfunction, high Expanding Disability Status Scale (EDSS) scores, cognitive impairment, obesity, fatigue and other factors may contribute to the transition from CIS to .

risk factors for retu.

The typical clinical manifestations of CIS patients prone to MS outcome are detailed in Table ➤Typical MRI manifestations (especially the presence of asymptomatic lesions) that are consistent with the characteristics of MS lesions are the most important hints for predicting the transformation of CIS to .

The characteristics of these lesions include: (1) diameter >3mm, regular shape, and clear boundary (2) Paraventricular lesions close to the lateral ventricle; (3) Subtentorial lesions: often appear in brainstem and cerebellar lesions, most commonly in the pons; (4) Spinal cord lesions: lesions >3mm and <2 vertebral segments , <1/2 of the spinal cord area on the cross section, generally mild edema; (5) Optic nerve lesions: short length of involvement, generally not involving the optic chiasm, optic nerve atrophy or asymptomatic characteristic images of optic neuritis (MRI lesions or RNFLT Thinning); (6) Near cortical lesions close to gray matt.
In addition to the characteristics of the lesions, the number of lesions is also a risk factor for the transformation of CIS to MS, especially ≥3 periventricular lesions are the risk factors for the transformation of CIS to .

It should be noted that six months and two years after the diagnosis of CIS, the probability of new clinical symptoms or active MRI lesions is 60%-70% and 80%-90%, respective.

Therefore, patients with CIS should not only be followed up for the presence of new nerv.

Systemic symptoms, regular follow-up with contrast-enhanced MRI is also recommended for early detection of evidence of disease activity or recurrence (Figure
 Figure 1 ➤ CSF OCB Positive CSF OCB is a strong predictor of CIS progression to .

For some typical CIS with multiple spatial evidence, if OCB is positive, other indicators of cerebrospinal fluid are consistent with MS manifestations, and there is no other more reasonable etiology, MS can be directly diagnos.

If the patient has MRI lesions consistent with MS, but not with spatial multiple, such as OCB positive, it indicates that the prognosis of MS is more like.

 ➤ Other CIS patients with abnormal vision, somatosensory, and brainstem evoked potentials (especially those with concurrent abnormalities), and decreased RNFLT on OCT may be more likely to develop .

➤Recommendation: stratify the risk of CIS to CDMS outcome based on the existing evidence and clinical ease of operation: (1) with typical clinical syndrome (Table 1); (2) with typical lesions consistent with MS Characteristic MRI lesions; (3) MRI showed lesions involving multiple typical sites at the same time; (4) ≥3 paraventricular lesions; (5) OCB positive in cerebrospinal flu.

Low risk: both (1) and (2); medium risk: both (1), (2), and (4); high risk: both (1) and (2), and (3) or (5) ) any of th.
➤Recommendation: For CIS patients who do not have risk factors for the progression to MS, it is recommended to evaluate whether CIS patients have the risk of developing CIS by identifying the core clinical syndromes, imaging features, and specific antibody status of other demyelinating diseases (Table
The possibility of other demyelinating disease outcomes, and follow-up to monitor their clinical outcom.

 Treatment of CIS ➤ Treatment principles Some patients with CIS have mild clinical symptoms, which can be relieved spontaneously after rest or symptomatic treatment, and hardly require treatme.

Aggressive treatment is often required when patients present with severe vision loss, optic neuritis with or without pain, marked dyskinesia due to spinal or brainstem syndrome, ataxia, or verti.

Treatment for CIS is similar to treatment for .

The following recommendations are made for the treatment of CIS from four aspects: acute treatment, remission treatment, symptomatic treatment and rehabilitation treatme.

 ➤Acute treatment There is currently no high-grade evidence specifically for the acute treatment of C.

Its treatment can refer to the acute treatment of .

 Treatment goals: relieve symptoms, shorten the course of disease, improve prognosis, and prevent complicatio.

 Main drugs and usage: Glucocorticoids are the first-line treatment of choi.

The principle of hormone therapy in the acute phase of CIS is high dose and short course of treatment (same as M.

Adults start from 5~0g/d, intravenous drip for 3~4h, a total of 3~5d, if the clinical neurological deficit is obviously recovered, it can be stopped direct.

If the recovery of clinical neurological deficit is not obvious, it can be changed to oral prednisone acetate or prednisolone 60~80mg, once a day, and reduce 5~10mg every 2 days until it is stopp.

In principle, the total course of treatment No more than 3-4 wee.
When there is a clear exacerbation of the disease (exact symptom exacerbation, new signs, imaging changes) during the process of steroid reduction, another high-dose steroid pulse therapy or second-line therapy can be consider.

Common adverse reactions of high-dose hormone therapy include obesity, electrolyte imbalance, blood sugar, blood pressure, dyslipidemia, peptic ulcer, osteoporosis, and femoral head necros.

 When hormone therapy is ineffective or the patient cannot tolerate hormone therapy, other treatments (second-line therapy) may be considered, including plasma exchange or intravenous gamma globul.

At present, there is no effective evidence for the efficacy of intravenous gamma globulin in the acute phase of CIS, and it can be used as an alternative treatment in pregnant and lactating women, and in patients with CIS who have failed hormone thera.

The recommended usage of the two can refer to the Chinese expert consensus on the diagnosis and treatment of MS (2018 editio.

➤Recommendation: For patients with important neurological deficits in the acute phase of CIS, it is recommended that the first choice of steroid pulse therapy be given; for other mild patients, clinical observation and corresponding symptomatic treatment can be temporarily perform.

 ➤Treatment in remission The treatment goal of CIS in remission: to delay the time for CIS to transform into CDMS, and to delay the disease progression of subsequent .

 Applicable population and treatment timing: For patients with high risk factors for MS outcome, early DMT is recommend.

Considering the clinical ease of operation, DMT is especially recommended for CIS patients with typical MSMRI lesions or positive cerebrospinal fluid O.

During the remission period of CIS patients, it is recommended to choose appropriate DMT treatment drugs based on the evidence-based medicine and comprehensive consideration of the patient's specific condition, drug efficacy and safety, ease of use, and patient complian.
During the use of DMT, it is necessary to provide patients with clinical follow-up management for assessment, monitoring of adverse drug reactions and toxic effects, and timely treatment of problems in treatment, so as to maintain good compliance and benefit patien.

Recombinant human interferon β-1b for injection: (1) Recommended usage: 250μg, subcutaneous injection, once every other d.

The starting dose is 65 μg, subcutaneously, once every other day, and after each injection, it is increased by 65 μg until the recommended do.

(2) Common adverse reactions: flu-like symptoms, local reactions at the injection site, leukopenia, elevated transaminases, abnormal thyroid function,e.

Teriflunomide: (1) Recommended usage: 7mg or 14mg, orally, once a d.

(2) Common adverse reactions and contraindications: increased alanine aminotransferase and total bilirubin, hair loss, diarrhea, paresthesia, upper respiratory tract infection,e.

Sinimod: (1) Recommended usage: The drug titration method and maintenance dose (1mg or 2mg, orally, once a day) need to be selected according to the patient's CYP2C9 genoty.

Contraindicated in patients with CYP2C9*3*3 genoty.

The specific use of the drug can be consulted with relevant clinical exper.

(2) Common adverse reactions: headache, increased blood pressure, slowed heart rate or atrioventricular block, liver damage, macular edema, risk of infection (herpes zoster, bronchitis, upper respiratory tract infection, e.

), decreased respiratory function, stopped Increased disability after treatme.

Dimethyl fumarate: (1) Recommended method: The initial dose is 120 mg, orally, twice a d.

After 7 days, the dose was increased to a maintenance dose of 240 mg, twice a d.
If intolerance to the maintenance dose, a temporary dose reduction to 120 mg twice a day may be consider.

Return to 240 mg twice daily within 4 wee.

If recovery to maintenance dose is still not tolerated, discontinuation of this product should be consider.

(2) Common adverse reactions: flushing, gastrointestinal symptoms (abdominal pain, diarrhea, nausea, vomiting), immediate allergic reaction and angioedema, lymphopenia, liver damage, progressive multifocal leukoencephalopathy, herpes zoster and other serious opportunistic infectio.

Taking with meals can reduce the incidence of flushi.

The specific use of the above drugs can be consulted with relevant clinical exper.

 In addition to the above four drugs, the following two DMT drugs can be used for the treatment of CIS: recombinant human interferon β-1a and glimepiride aceta.

 ➤Recommendation: For CIS patients who meet the 2017 revised McDonaldMS diagnostic criteria, early initiation of DMT is recommended when other possible diagnoses are clearly exclud.

For high-risk CIS patients, DMT is recommended under the premise of full communication with the patie.

DMT treatment of CIS needs to comprehensively consider many factors such as drug efficacy, long-term safety, ease of use, patient compliance, and evidence-based medici.

 ➤ For symptomatic treatment recommendations, refer to the Chinese Expert Consensus on the Diagnosis and Treatment of MS (2018 Editio.

 ➤Rehabilitation treatment, health education and psychological support recommendations refer to the Chinese expert consensus on MS diagnosis and treatment (2018 editio.

 ➤Recommendation: Attention should be paid to symptomatic treatment, rehabilitation, psychological support and disease knowledge education for CIS patients to improve the quality of life and treatment compliance of patients
 ➤Treatment evaluation and follow-up process After a diagnosis of CIS, physicians should keep in touch with patients and follow up regularly to monitor disease activity, provide drug therapy, and suppo.

Regardless of whether DMT is started or not, it is recommended to review the head MRI scan every 6 to 12 months (the same sequence and scan parameters are strongly recommended) for 5 consecutive years; there is no mandatory requirement for spinal cord MRI follow-.

The process of diagnosis and treatment and follow-up of CIS is shown in Figure➤Recommendation: All CIS patients should undergo standardized clinical and imaging follow-up after diagnosis to detect disease activity, disease outcome early, and monitor drug efficacy and safe.

 Yimaitong is compiled from: Neuroimmunology Group, Neurology Branch of Chinese Medical Associati.

Chinese expert consensus on the diagnosis and treatment of clinically isolated syndrome (2021 editio.

Chinese Journal of Neurology, 2022, 55(4): 280-28