Initial Manifestation Of Multiple Sclerosis Research Articles

Incidence of Optic Neuritis among Omani Patients with Multiple Sclerosis at the Sultan Qaboos University Hospital, Muscat, Oman

Objectives: Multiple sclerosis (MS) is a chronic, multifaceted, heterogeneous autoimmune disease, with optic neuritis (ON) being a common early manifestation among those with MS. This study aimed to estimate the incidence of ON among Omani patients with MS. Methods: This retrospective cross-sectional study included all Omani patients diagnosed with MS at the Sultan Qaboos University Hospital, Muscat, Oman, between January 1991 and December 2019. The data were collected from the neurology registry and electronic medical records and analysed descriptively using univariant and multivariant statistical techniques. Results: Out of the 185 patients diagnosed with MS during the study period, 170 were included in the analysis. The male-to-female ratio was 1:2 and the mean age was 28 years. The incidence of ON in the population was 28.8%, with 83.7% of ON patients presenting with relapse-remitting MS (RRMS). Overall, 28.6% of patients presented with O N as an initial manifestation of MS, whereas 42.8% developed ON at a later stage. Most patients (49.4%) were from higher-latitude regions of Oman such as Muscat and Al Batinah. Conclusions: The incidence of both MS and ON increased over the study period. While the overall incidence was low in comparison with Western data, it was similar to the rates reported elsewhere in the Arabian Peninsula. Overall, ON was the most common manifestation of MS in the cohort, with younger female patients more frequently presenting with both MS and ON. A significant association was found between the RRMS subtype and ON presentation. Keywords: Demyelinating Diseases; Optic Neuritis; Multiple Sclerosis; Relapsing-Remitting Multiple Sclerosis; Incidence; Epidemiology; Oman.

Complete Bilateral Horizontal Gaze Palsy as Initial Manifestation of Multiple Sclerosis: A Case Report

Complete Bilateral Horizontal Gaze Palsy as Initial Manifestation of Multiple Sclerosis: A Case Report

Development of a Prognostic Model for Predicting Multiple Sclerosis After Optic Neuritis: A Secondary Analysis of Data From the Optic Neuritis Treatment Trial.

Optic neuritis can be the initial manifestation of multiple sclerosis (MS). The purpose of this study was to develop a prognostic model for predicting the risk of MS development among patients with optic neuritis. The data from 388 patients with optic neuritis were retrieved from the Optic Neuritis Treatment Trial (ONTT). Cox proportional hazards regression analysis was used to develop a prognostic model. The performance of the model was assessed by using Harrell's C-index and calibration curves. The rates of MS development were estimated using the Kaplan-Meier method. Among the enrolled subjects, a total of 154 (39.7%) patients developed clinically definite MS during a median follow-up period of 15.8 years (interquartile range, 7.2-16.9 years). The factors associated with the development of MS were the presence of brain lesions as on baseline MRI, previous nonspecific neurologic symptoms, commencing low-dose corticosteroids treatment, ocular pain, and absence of optic disc/peripapillary hemorrhage. After incorporating these 5 factors into the prognostic model, a C-index of 0.72 (95% confidence interval [CI], 0.69-0.76) and good calibration curves were obtained. The C-index of the model was significantly higher than the C-indexes of any single factor (P < 0.001 in all cases). The model was able to stratify the ONTT patient cohort into 3 risk groups with significantly different intergroup rates of developing MS (rates for developing MS within a 15-year period: high-risk group, 75.7% [95% CI, 65.6%-82.9%], intermediate-risk group, 44.7% [95% CI, 31.4%-55.4%]; and low-risk group, 20.8% [95% CI, 14.2%-26.8%]; log-rank P < 0.001). This prognostic model had a better prediction ability when compared with the standard practice that relies solely on using brain lesions on MRI. It can, therefore, help guide decision-making to initiate earlier disease-modifying therapy for patients with optic neuritis at risk of developing MS.

Secondary cluster headache due to a contralateral demyelinating periaqueductal gray matter lesion

Tension-type headache and migraine without aura are the most common primary headaches occurring in people with demyelinating diseases, whereas cluster headache (CH) can be considered exceptional. The location of demyelinating lesions could be strategic in these cases, involving areas interacting with the trigeminovascular system. We report a case of a 54-year-old woman with right-sided CH as the initial manifestation of multiple sclerosis and showing a left dorsal brainstem lesion on magnetic resonance imaging, in the region of the dorsal longitudinal fasciculus (DLF). Our case seems to suggest a possible role of the DLF in the process that leads to CH attacks. Because neuroimaging clearly showed a lesion contralateral to CH pain, we hypothesize that some fibers from periaqueductal gray matter project to the contralateral side, besides the known ipsilateral connections.

Complete Bilateral Horizontal Gaze Palsy as Initial Manifestation of Multiple Sclerosis: A Case Report

Multiple sclerosis is a chronic inflammatory disease of central nervous system that commonly affects young adults. Although ocular movement disturbances are commonly encountered in multiple sclerosis, bilateral horizontal gaze palsy is quite rare. We present a case of young woman presented with dizziness, intractable vomiting and visual disturbances for one week, on examination found to have complete bilateral horizontal gaze palsy while vertical gaze was intact. Brain MRI showed a small lesion in posterior part of medial pontine tegmentum bilaterally which was responsible for patient`s symptoms. She received five doses of one-gram methylprednisolone, her symptoms gradually improved over one week after treatment.

Anisocoria as initial manifestation of multiple sclerosis. Use of 3 tesla magnetic resonance imaging

Abstract A 21-year-old woman seen in this clinic with non-reactive mydriasis in the right eye that contracted with 1% pilocarpine. Cranial angio-CT and 1.5 T magnetic resonance imaging (MRI) did not detect any disease. Given a subsequent limitation of adduction, supraduction, and infarction of the right eye, a 3 T MRI was requested. This showed a lesion of the midbrain at the exit of the 3rd cranial nerve. After improvement, no new episodes were observed until 18 months later, when the patient presented with probable optic neuritis and systemic symptoms. At this time the 1.5 T MRI detected infratentorial and supratentorial demyelinating plaques. A subsequent lumbar puncture and clinic outcome confirmed the diagnosis of relapsing-remitting multiple sclerosis.

Should Spinal MRI Be Routinely Performed in Patients With Clinically Isolated Optic Neuritis?

Should Spinal MRI Be Routinely Performed in Patients With Clinically Isolated Optic Neuritis?

Color vision testing versus pattern visual evoked potentials and optical coherence tomography parameters in subclinical optic nerve involvement in multiple sclerosis

Acute idiopathic demyelinating optic neuritis is frequently the initial manifestation of multiple sclerosis (MS). We aimed to discuss the value of color vision testing to detect possible optic nerve involvement in patients with MS who had no history of optic neuritis. We evaluated color vision with Farnsworth-Munsell 100 (FM-100) hue test. Total error scores (TES), partial error scores for the red-green axis (RGS) and blue-yellow axis (BYS) were calculated. Topographic optic disc parameters (RNFL, RA, DA, CV, RV, and vertical C/D ratio), total macular volume (TMV), central macular thickness (CMT), and retinal ganglion cell layer (RGCL) were determined using spectral domain optical coherence tomography (SD-OCT). Choroidal thickness (CT) was measured using enhanced depth imaging optical coherence tomography (EDI-OCT). Pattern visual evoked potentials (PVEP) were also performed. Twenty-eight patients with RRMS (56 eyes) and 25 healthy controls (50 eyes) were included. P100 latencies were significantly delayed and P100 amplitudes were significantly reduced in the patient group compared with the controls (p ≤ 0.05). Statistically significant thinning was found in temporal quadrant in the patient group compared with the controls (p = 0.002). TES RGS, and BYS were all increased in the patient group but this was not statistically significant. We found no correlation between TES, RGS, BYS, and P100 latencies or OCT parameters. In our investigation as to whether color vision testing could be a simple biomarker for showing neurodegeneration of the anterior visual pathway regardless of optic neuritis, PVEP and OCT-assessed RNFL thickness seemed to be a more valuable biomarker than color vision testing.

Hesperetin reduces myelin damage and ameliorates glial activation in lysolecithin-induced focal demyelination model of rat optic chiasm

Visual impairment is considered as the most common initial manifestation of multiple sclerosis (MS) patients. It has been shown that hesperetin (Hst), a flavonoid of citrus fruit, possesses anti-inflammatory and antioxidant effects both in vitro and in vivo. The present study was designed to evaluate the pharmacological/medicinal effects of Hst treatment on myelin repair and glial activation in lysolecithin (LPC)-induced focal demyelination model. In order to induce local demyelination model, LPC 1% (2 μL) was injected into the optic chiasm of rats. Animals received oral administration of Hst at dose of 20 mg/kg for 14 or 21 days post lesion induction. Visual evoked potential (VEP) recordings were conducted before and also on days 7, 14 and 21 post LPC injection. Glial activation and myelination of optic chiasm were evaluated by immunostaining on brain sections. Analysis of VEPs data revealed that oral administration of Hst effectively reduced the latency of N1 waves. Immunostaining results showed the reduced number of astrocytes and microglia in animal which were treated with Hst. Furthermore, the extent of demyelination area was decreased in animals treated by Hst. Taken together; our results suggest that Hst treatment significantly protects and repairs myelin sheath, therefore it might be regarded as effective supplementary agent in demyelinating disorders, particularly MS.

Paroxysmal and unusual symptoms as first clinical manifestation of multiple sclerosis do not indicate benign prognosis-The PaSiMS II study.

BackgroundParoxysmal (PS) and unusual symptoms (US) account for approximately 1.6% of initial manifestations of multiple sclerosis (MS) and have comparable conversion rates to clinically definite MS (CDMS) as classical bout onset symptoms (CS). However, long-term prognosis and clinical outcome of patients experiencing PS or US as first clinical manifestation are unclear.MethodsClinical, MRI and cerebrospinal fluid data were obtained retrospectively and patients presenting with PS or US were compared to patients with CS presentation.ResultsIn a cohort of 532 relapsing onset MS patients followed for a mean period of 11.4 years (SD 3.6), 10 (1.9%) patients initially presented with PS/US. PS/US patients received disease modifying treatment (DMT) in a significantly smaller proportion immediately after the first clinical symptom (30% vs. 61.7%; p = 0.021) and during the observation period (60% vs. 83.5%; p = 0.033). In multivariate models correcting for sex, age at initial symptoms, complete remission of initial symptoms, total number of T2 and contrast-enhancing lesions, presence of oligoclonal bands and DMT exposure, PS/US were not associated with lower annualized relapse rate or lower EDSS over time.ConclusionIn addition to a similar conversion rate to CDMS, patients presenting with PS/US at disease onset display very similar relapse and disability rates as patients with CS onset. Consequently, initial presentation with PS/US does not indicate benign or atypical MS, but requires DMT initiation based on the same criteria as in CS patients.

Prediction of Multiple Sclerosis after Childhood Isolated Optic Neuritis

Isolated optic neuritis in adults (ON) is the most common initial manifestation of multiple sclerosis (MS). Conversion to MS after childhood ON is not well determined. We aimed to identify risk factors predicting MS following ON and to develop risk profiles with adjusted clinical follow-up based on current diagnostic tools. Medical records of 42 cases with isolated ON between 1970 and 2005 were analysed. In 2006 and 2007 all patients received a clinical follow-up investigation including ophthalmological and neurological examination, visual evoked potentials (VEPs), somatosensory evoked potentials (SEPs) and cerebral magnetic resonance imaging (cMRI). Investigation was performed to a mean follow-up of 18 years (3-38 years). 14% of all patients showed MS-like lesions in cMRI. Additional neurologic symptoms or abnormal cMRI at initial presentation indicating dissemination in space significantly altered the risk of MS (OR 16.0, 95% CI [1.5; 176.5], p = 0.020), (OR 4.6, 95% CI [0.7; 31.0], respectively). Severe visual loss and funduscopic affection reduced the likelihood for progression to MS (OR 0.2, 95% CI [0.0; 1.5]). Children presenting with isolated ON, neurological impairment at onset or especially coordinative dysfunction at follow-up and demyelinating lesions in cMRI at disease onset were at high risk for the development of MS.

Rethinking the importance of paroxysmal and unusual symptoms as first clinical manifestation of multiple sclerosis: They do matter

BackgroundParoxysmal (PS) and unusual symptoms (US) as initial manifestation of multiple sclerosis (MS) are rare and often thought to indicate “benign” MS. ObjectiveTo investigate prevalence and clinical disease course of patients experiencing PS or US as first clinical manifestation. MethodsClinical, MRI and cerebrospinal fluid data of patients presenting with PS and US were obtained retrospectively and compared to patients with classical bout onset (CS). ResultsIn a cohort of 1396 relapsing onset patients, 15 (1.1%) were identified as presenting with PS and 7 (0.5%) with US. Groups were comparable regarding gender, age at onset and intrathecal immunoglobulin synthesis (p>0.05). During a mean follow-up period of 13.6 years, all patients presenting with PS or US converted to CDMS (mean duration 3.4 years; 95% CI 1.9–4.8) as compared to 1374 patients (94%) presenting with CS (mean duration 3.2 years; 95% CI 3.0–3.4; p=0.759). ConclusionIn a cohort of 1396 MS patients, 1.6% presented with PS or US at disease onset. Irrespective of the initial transient symptoms, patients were at the same risk of developing CDMS as CS patients, thereby underlining the importance of identifying PS and US as possible first clinical symptoms of MS.

Rare onset symptoms in multiple sclerosis

Introduction: Multiple sclerosis (MS) may present with unusual manifestations such as pain syndromes, movement disorders, rare cranial nerve involvement, cognitive or psychiatric symptoms, leading to diagnostic dilemma. The purpose of this study is to determine the types of rare onset symptoms in patients with MS in order to provide better clues for early diagnosis.Method: We, retrospectively, analysed data of 680 MS patients who were diagnosed or followed-up in our demyelinating diseases unit. Onset symptoms such as visual field defects, rare cranial nerve involvement, paroxysmal symptoms, movement disorders, pain syndromes, cognitive and psychiatric manifestations were recorded.Results: Nineteen MS patients (13 women) were identified as having unusual initial manifestations. None of these cases had typical optic, brainstem, sensory, motor or cerebellar signs. Five patients presented with rare cranial nerve involvement, five patients with pain syndromes, four patients with movement disorders, two patients with paroxysmal symptoms, two patients with cognitive deficits and one patient with homonymous hemianopia. None of these patients were diagnosed with MS at initial presentation; all of them were diagnosed with MS in the following months or years.Conclusion: This retrospective study indicates that there is a wide range of rare initial manifestations of MS due to diverse involvement of central nervous system. Rare, unusual symptoms complicate early diagnosis. Given the fact that disease modifying treatment should be initiated early, it is crucial to diagnose MS as early as possible. Therefore, physicians should not disregard MS when a patient presents with any of these rare manifestations.

Treatment of Optic Neuritis

Optic neuritis (ON) is a self-limiting condition caused by inflammation-driven demyelination process affecting the optic nerve. Main clinical features are sudden, unilateral worsening of visual acuity, colour vision disturbance, visual field defects and motion-induced ocular pain. Spontaneous recovery appears usually within up to 8 weeks. It is a frequent initial manifestation of multiple sclerosis. Treatment of optic neuritis remains controversial, although many clinical trials have been conducted to establish firm therapeutic guidelines. The most relevant clinical trial is the Optic Neuritis Treatment Trial (ONTT), proving three days’ intravenous methylprednisolone therapy is not able to change the long-term prognosis, however improving visual recovery, what became a therapeutic option in monocular patients, patients with significant visual field loss, as well as those with professional requirements of fast visual recovery. The ONTT showed that 15-year risk of developing multiple sclerosis was 50 % regardless of the treatment regimen. Oral corticosteroids are recommended for treatment of acute optic neuritis.

Cluster-tic syndrome as the initial manifestation of multiple sclerosis

We report the case of a patient diagnosed as having cluster-tic syndrome as the initial manifestation of multiple sclerosis (MS). The patient’s headache bouts improved after treatment with antiepileptic drugs, steroids, and beta-interferon. Magnetic resonance imaging (MRI) scans showed a pontine demyelinating lesion involving the area of the trigeminal root inlet and main sensory nucleus. Neurophysiological studies correlated well with MRI lesions. The association between cluster-tic syndrome and MS is an exception, and the mechanism of the pain is still unknown; therefore, this case might suggest a pathophysiological relationship between the trigeminal main sensory nucleus and cluster-tic syndrome.

Chiasmal optic neuritis: A report of three cases

Chiasmal optic neuritis (ON), a rare condition that affects the optic chiasm, is mostly associated with inflammatory demyelinating disorders and may be the initial manifestation of multiple sclerosis (MS). Here, we reported three cases of MS with chiasmal optic neuritis. The clinical manifestations, neuroimaging results, and visual prognosis were evaluated in each patient. Routine eye examinations and auxiliary examinations, including Ishihara color plate, determination of the visual field (VF), and magnetic resonance imaging (MRI) of the optic nerve and chiasm, were performed. All patients presented with reduced VA and VF defects. The abnormal enhancement of the optic chiasm was clearly demonstrated on MRI. Two patients recovered after the systemic administration of steroids, but the other patient only partially recovered. In conclusion, although it is rare, chiasmal ON should be considered in patients who develop bitemporal hemianopia. MRI is the modality of choice for accurate diagnosis. Early diagnosis and proper treatment are mandatory for the restoration of restore visual function.

P-248 - A bipolar affective disorder prior to the unset of a multiple sclerosis: a case report

Multiple sclerosis is a chronic neurological disease characterized by a demyelinating process in the central nervous system. Psychiatric symptoms, and especially mood disorders, occur more frequently in multiple sclerosis than in other chronic diseases. To report the occurence, type, MRI abnormalities and management of a bipolar affective disorder prior to the onset of multiple sclerosis. We report a case of a forty-one-years old man, who developed a manic episode induced by antidepressant treatment, four months before the diagnosis of multiple sclerosis. This case report suggests that bipolar affective disorders may be the initial manifestations of multiple sclerosis. The awareness of psychiatric manifestations in unset and acute relapse episodes of multiple sclerosis may be helpful for an early dagnosis and for treatment adjustment.

The role of the Epstein-Barr virus in the pathogenesis of some autoimmune disorders — Similarities and differences

After a brief summary on the properties of the Epstein-Barr virus (EBV), the course and latency stages of the infection, the characteristics of infectious mononucleosis (IM), and other disorders caused by this virus, as well as the course of the serological responses to EBV, the current paper focuses on the role of EBV in two autoimmune disorders: multiple sclerosis (MS), and systemic lupus erythematosus (SLE). Diverse evidence suggests that infection by EBV during late childhood or young adulthood may have a role in the pathogenesis of MS. These include the similarity between the geographical distribution of IMand MS, the high risk of contracting MS by individuals who have recovered from IM, the elevation of the titers of IgG antibodies against EBV nuclear antigens occurring years before the initial manifestations of MS, and the extremely rare occurrence of MS in individuals seronegative for EBV. However, the data on the mechanism underlying the relationship between EBV and MS are controversial. Moreover, many observations indicate that EBV contributes also to the pathomechanism of SLE. However, this contribution differs from the relationship between EBV and MS, as shown by the lack of any increase in the risk of SLE after IM. In SLE, EBV serology is quantitatively and qualitatively different from the normal response - that is, EBV viral load is higher and a strong cross-reaction can be detected between certain EBV antigens and autoantigens of pathological importance. These observations, along with the findings pointing to a possible role of EBV in rheumatoid arthritis and myasthenia gravis indicate that infection by EBV may be one of the environmental factors, which can facilitate the development of some autoimmune disorders in genetically susceptible individuals.

Symptomatic paroxysmal kinesigenic choreoathetosis as primary manifestation of multiple sclerosis

Paroxysmal kinesigenic choreoathetosis (PKC) is a rare movement disorder characterized by episodes of unior bilateral choreoathetosis precipitated by sudden or rapid movements, startle or hyperventilation. It can be categorized as primary, e.g. idiopathic or hereditary, and secondary PKC [3]. Amongst the more frequent causes of the latter is multiple sclerosis (MS) [1]. Here we describe two patients presenting with symptomatic PKC as a clinically isolated syndrome. Patient 1, a 34-year old woman, presented with a twoweek history of episodes of right-sided numbness, tingling and spasms of her hand and leg occurring 2–15 times a day for 60 s per episode. These episodes were triggered by sudden movements, e.g. turning her head or moving in bed. Patient 2, a 27-year old woman, experienced multiple ([50) daily episodes of painful spasms of her right arm and leg as well as ‘‘pressed’’ speech for a period of about 1 min triggered by repetitive movements or hyperventilation. In between attacks, only light muscle soreness was reported. Neurofibromatosis I had been diagnosed previously in her and her father. No other medical conditions, medications or previous visual, motor or sensory episodes were reported in either patient and there was no family history of movement disorders. Neurological examination at rest was normal in both patients. When running on the spot, jumping or hyperventilating, right-sided paroxysmal choreoathetosis developed gradually and disappeared within 60 s in both patients. In addition, left-sided brachial and axial dystonia, orofacial chorea and ‘‘pressed’’ dysarthria accompanied the episodes in patient 2. MRI showed a contrast-enhancing lesion in the left dorsolateral thalamus in patient 1 and a lesion in the left mesencephalic peduncle in patient 2 (Fig. 1). In patient 1 ten, and in patient 2 two supratentorial suband juxtacortical T2 lesions were observed. Follow up MRI in patient 1 revealed a novel cervical spinal cord lesion, thus leading to diagnosis of MS because of temporal and spatial dissemination [5]. In patient 2, follow up investigations have not yet been performed. CSF analysis showed oligoclonal bands, \40 cells/ll and normal total protein and albumin ratio in both patients. Steroids led to prompt remission of episodes within 2 days. Symptomatic PKC is a very rare initial manifestation of multiple sclerosis [2, 6]. To our knowledge these two cases represent the first video documentation of symptomatic PKC in this setting. In contrast to primary PKC which is characterized by immediate onset of choreoathetosis after sudden movements symptoms in our patients gradually developed over a couple of seconds during movements or hyperventilation. In our patients PKC was caused by lesions in the dorsolateral thalamus and mesencephalic peduncle. In patient 1, Gd-enhancement of the thalamic lesion was still observed at presentation and in both patients symptoms disappeared rapidly after antiElectronic supplementary material The online version of this article (doi:10.1007/s00415-011-6188-5) contains supplementary material, which is available to authorized users.

Paroxysmal Dystonia as a Rare Initial Manifestation of Multiple Sclerosis

Multiple sclerosis is an uncommon disease in childhood and adolescence and is rarely associated with movement disorders other than tremor. The differential diagnosis is difficult to establish when, particularly, movement disorder presents as the initial manifestation of multiple sclerosis. Video-electroencephalography monitoring is the gold-standard method for the differential diagnosis of epileptic and paroxysmal nonepileptic events, including movement disorders and psychogenic seizures. This article presents a patient with paroxysmal dystonia secondary to multiple sclerosis who previously was diagnosed and treated as having conversion disorder and epilepsy. The utility of video-electroencephalography monitoring during the process of differential diagnosis is discussed.