Consensus recommendations for the diagnosis and treatment of multiple sclerosis in Kuwait.

OBJECTIVES: We aim to develop consensus recommendations to guide neurologists in the community for the diagnosis and treatment of Multiple Sclerosis (MS). METHODS: After reviewing the available literature, a group of neurologists with expertise in MS met to discuss the evidence and develop consensus recommendations for the diagnosis and treatment of MS. RESULTS: The revised 2010 McDonald criteria is the established diagnostic criteria for MS and has wide international acceptance among international MS experts. Several red flags in the history and examination, along with certain laboratory tests were pointed out to exclude MS mimickers in the diagnostic phase. The available approved disease modifying therapies (DMTs) were listed in an algorithmic fashion based on initial assessment of disease severity and subsequent disease breakthrough while on DMTs. Risk stratification based on the benefit versus risk ratio was used to help choosing the appropriate therapy to MS patients using an "individualized therapy" approach. The requirements for initiation and monitoring of treated MS patients were highlighted with emphasis on early identification of disease breakthrough, adverse events, and safety concerns. The role of multi-disciplinary MS clinics was discussed and a guide for referral to specialized MS clinics was developed. CONCLUSIONS: Consensus recommendations have been developed to guide local neurologists on the diagnosis and treatment of patients with MS. Implementation of the revised 2010 McDonald diagnostic criteria was advised while a personalized treatment approach was recommended using a treatment algorithm based on risk stratification and patient-centered outcomes.

Multiple sclerosis reactivation postfingolimod cessation: is it IRIS?

Although few recent studies have reported efficacy and safety data among patients with multiple sclerosis (MS) switching between immunotherapies, data on the mechanism of rebound activity postwithdrawal of fingolimod in patients with MS is scarce. A 36-year-old woman developed severe reactivation of her disease within 7 weeks of fingolimod's withdrawal despite the absence of breakthrough disease during the 8-week natalizumab washout period previously. The clinical presentation and radiological features were described indicating the diagnostic challenge given the potential risk of developing progressive multifocal leucoencephalopathy. The severe reactivation postwithdrawal of fingolimod could be due to the immune reconstitution inflammatory syndrome (IRIS) given the abrupt rise in lymphocyte count. Patients who discontinued fingolimod might be at risk of developing IRIS resulting in disease reactivation in the washout period.

Increasing prevalence and incidence rates of multiple sclerosis in Kuwait.

BACKGROUND: Kuwait was considered as low to intermediate risk area for MS. OBJECTIVES: To determine the prevalence and incidence rates of MS among Kuwaiti nationals based on 2011 population census. METHODS: This cross-sectional study was conducted between October 2010 and April 2013 using the newly developed national MS registry in Kuwait. Patients with a diagnosis of MS according to 2010 revised McDonald criteria were identified. The crude, age- and sex-specific prevalence and incidence rates among Kuwaiti patients were calculated. RESULTS: 1176 MS patients were identified of which 927 (78.8%) were Kuwaitis and 249 (21.2%) were expatriates. Among Kuwaiti patients, female to male ratio was 1.8:1 with a mean age of 35.40 ± 10.99 years. The prevalence rate of MS was 85.05 per 100,000 persons (95% CI: 82.80 - 87.04). There was a peak in prevalence among patients aged 30-39 years. The incidence of MS was 6.88 per 100,000 persons (95% CI 5.52-8.55). Between 2003 and 2011, the incidence increased 3.22 and 2.54 times in women and men respectively. CONCLUSION: Kuwait is considered a high-risk area for MS. The significant increase in prevalence and incidence rates may represent a true increase despite the improvement in case ascertainment and case definition.

Use of natalizumab in patients with active relapsing-remitting multiple sclerosis in Kuwait.

OBJECTIVE: To evaluate the outcomes of patients with multiple sclerosis (MS) who were treated with natalizumab in Kuwait. MATERIALS AND METHODS: A retrospective study using the MS registry to identify patients who were treated with natalizumab was conducted. Patients' demographics, clinical characteristics and treatment parameters were collected at baseline and last follow-up visit. Primary outcome was the proportion of relapse-free patients at the last follow-up while secondary outcomes were the change in the mean annual relapse rate, Expanded Disability Status Scale (EDSS) and the proportion of patients with magnetic resonance imaging (MRI) activity at the last follow-up visit. Forty-four patients were included in the study. RESULTS: Of the 44 patients, 27 (61.4%) were females and the remaining 17 (38.6%) males. Mean age of patients and mean disease duration were 29.05 ± 7.25 and 5.71 ± 3.37 years, respectively. The mean number of natalizumab infusions was 18.14. The proportion of relapse-free patients significantly increased from 11.36 to 90.91% (p < 0.0001). The EDSS significantly improved from 4.76 to 3.15 (p < 0.0001) over the observational period. There was no significant difference between patients with EDSS <3 compared to those with EDSS ≥ 3 (p < 0.67). The proportion of patients with MRI activity was significantly reduced from 95.5 to 18.2% (p < 0.0001) at their last visit. Six patients discontinued the drug, 5 due to positive JC virus and 1 due to pregnancy. CONCLUSIONS: Natalizumab induced a suppression of disease activity and was responsible for a significant improvement in disability status in highly active MS patients.

Endovascular treatment of chronic cerebrospinal venous insufficiency in multiple sclerosis: a retrospective study.

BACKGROUND: Chronic cerebrospinal venous insufficiency (CCSVI) has been proposed to be associated with multiple sclerosis (MS). Zamboni et al. reported significant improvement in neurological outcomes in MS patients who underwent percutaneous transluminal angioplasty (PTA). OBJECTIVES: To retrospectively evaluate the neurological outcomes in MS patients who underwent PTA. METHOD: Relapsing remitting MS patients who underwent PTA and completed at least 1 year post-PTA were assessed. Patients with clinically isolated syndrome or progressive forms of MS were excluded. Primary endpoint was the proportion of relapse-free patients at 1 year. Secondary endpoints were change in mean Expanded Disability Status Scale (EDSS) score and proportion of patients with new magnetic resonance imaging (MRI) activity (defined as either gadolinium-enhancing or new T2 lesions) at 1 year. RESULTS: Forty-five patients satisfied the inclusion criteria. Females constituted 71.1%. The mean age and mean disease duration were 33.76 and 7.16 years, respectively. At 1-year post-PTA, the proportion of relapse-free patients decreased from 84.44% to 66.67% (p = 0.085), whereas the mean EDSS score increased (p = 0.017). The proportion of patients with new MRI activity increased significantly from 17.78% to 44.44% (p = 0.012). A total of 35.6% of patients stopped their disease modifying therapies (DMTs). There was no difference among the patients who stopped their DMTs with respect to relapses, EDSS score or new MRI activity. CONCLUSION: The study revealed that PTA in relapsing remitting MS patients was not associated with any neurological improvement. However, there was an increase in disease activity irrespective of the adherence to DMTs. Further evidence of the association between CCSVI and MS is required.

Albendazole therapy for single small enhancing CT lesions (SSECTL) in the brain in epilepsy.

BACKGROUND: Single small enhancing CT lesions (SSECTL) of the brain with or without perifocal oedema are common in patients with symptomatic epilepsy in India. Solitary cysticercus granuloma, a benign form of parenchymal neurocysticercosis, is considered to be the most common aetiology for SSECTL. Definite information is lacking regarding the effectiveness of antiparasitic treatment on resolution of these lesions and on long term seizure recurrence. OBJECTIVE: To evaluate the response to albendazole treatment in patients who had SSECTL and new onset seizures treated with antiepileptic drugs (AED) in a prospective clinical trial. METHODS: 43 patients who presented with new onset seizures and were documented to have SSECTL were alternatively allocated to receive albendazole 15 mg/kg/day for 2 weeks or no cysticidal therapy. All patients were treated with AED and followed for at least 6 months for seizure recurrence, and serial CT scans were obtained at 4 weeks, 3 months and at study completion. RESULTS: 28 (65%) patients were aged 5-25 years and 31 (72%) presented clinically with partial motor seizures with or without generalisation. Most of the SSECTL were ring lesions (75%) and located in and around the sensory-motor cortex at the gray-white junction (65%). In the albendazole group, 56% of patients compared with 35% in the control group showed resolution of SSECTL (p = 0.154) at 1 month. 22 of 23 patients (95.6%), who received albendazole, compared with 14 of 20 patients (70%) in the control group, demonstrated radiological resolution on study completion (p = 0.03). Punctate residual calcification and seizure recurrence were observed in four patients (9.3%) in the control group and in three (7%) patients in the albendazole group (p = 0.47). CONCLUSIONS: In patients presenting with seizures due to single viable parenchymal neurocysticercosis, albendazole hastens the resolution of SSECTL if treatment is given in the early phase of the illness.

Additional case of Ramichloridium mackenziei cerebral phaeohyphomycosis from the Middle East.

In this report we describe a case of cerebral phaeohyphomycosis involving a 56-year-old Egyptian male who worked as a mason in Kuwait for 6 years. Computerized tomography scan of the brain revealed presence of a large abscess in the left occipital lobe. Aspirated pus from the abscess showed branched, septate, hyphae with light brown pigmentation. Cultured pus grew the fungus Ramichloridium mackenziei. Despite amphotericin B (1 mg kg(-1) per day) therapy for 2 weeks, the patient expired. The isolate was later found to be resistant to amphotericin B ( > 32 microg ml(-1)). Antifungal susceptibility testing to other agents was also performed.

Acute symptomatic seizures due to single CT lesions: how long to treat with antiepileptic drugs?

The duration of anti epileptic drug therapy for single small enhancing CT lesions (SSECTL) presents a major dilemma. We studied the efficacy of short duration (6 months) antiepileptic drug therapy as compared to long duration (2 years) drug therapy. Seventy three patients presenting with seizures and showing SSECTL on cranial CT scans (plain and contrast) were randomized into group A (6 months therapy) and group B (2 years therapy). There were 47 patients in group A and 26 patients in group B. Patients were followed up for one year after withdrawal of anti epileptic drugs. CT Head (plain and contrast) was repeated after 3 months, or earlier in cases of recurrence to rule out reinfection. 53.2% in group A and 53.8% in group B showed complete resolution and were seizure free on one year follow up. Punctate residual calcification was seen in 46.8% in group A and 46.2% in group B. Eight patients (17%) in group A and three (11.5%) in group B had a recurrence. The difference in recurrence of seizure between the two groups was not statistically significant (p<0.77) in the calcified lesion subset. Since none of the patients in total resolution subset showed recurrence, the difference between calcified and total resolution subset was highly significant. The study shows that a short duration (6 months) AED therapy in patients with total resolution of lesion on follow up scan, may be adequate in comparison to those who have calcific speck as a residue. However, a longer duration of therapy in case of calcific group probably does not alter their chances of recurrence.

Albendazole therapy for solitary persistent cysticercus granuloma.

Use of Albendazole therapy for the treatment of patients having persisting intracranial solitary cysticercus granuloma is controversial. Most of the times these patients are treated empirically with variety of drugs for variable period. Some authors advocate biopsy before definitive treatment. 25 patients having radiologicaly persistent solitary cysticercus granuloma (>6 months) were given 15 days course of oral albendazole (15 mg/kg body wt). Cranial CT scan was repeated one month after the completion of albendazole therapy. It was evaluated for complete resolution, partial response (> 50% decrease in size of lesion) or no change as compared to previous scan. 12 patients (48%) showed complete resolution, 4 patients (16%) showed a partial response, while 9 patients (36%) did not show any change on follow up. Albendazole therapy may be useful for patients having persistent cysticercus granuloma.

Botulinum toxin treatment of hemifacial spasm and blepharospasm: objective response evaluation.

Twenty seven patients with hemifacial spasm (HFS) and sixteen patients with blepharospasm (BS) having mean Jankovic disability rating scale score of 2.56+0.58 SD and 2.81+0.54 SD, respectively, were treated with botulinum toxin A (BTX-A) injections. The total number of injection sessions were ninety one with relief response in 98.91%. The mean improvement in function scale score was 3.78+0.64 SD and 3.29+1.07 SD respectively, in HFS and BS groups. The clinical benefit induced by botulinum toxin lasted for a mean of 4.46+3.11 SD (range 2 to 13) months in HFS group and 2.66+1.37 SD (range 1 to 6) months, in BS groups. Transient ptosis was seen in 4.39% of total ninety one injection sessions. These findings show that local botulinum toxin treatment provides effective, safe and long lasting relief of spasms.

Pentazocine-induced fibromyositis and contracture.

We report a case of myopathy, accompanied by widespread contractures predominantly involving the elbow and knee joints, following long-standing pentazocine abuse.

Palatal myoclonus in postinfectious opsoclonus myoclonus syndrome : a case report.

An adult male presenting with acute onset opsoclonus, myoclonus and cerebellar ataxia is being reported. Patient had myoclonus involving limbs and palate. There are only a few reported cases associated with palatal myoclonus. Patient showed gradual spontaneous recovery. Possibility of underlying malignancy was excluded by detailed investigations.

Clinical profile of multiple sclerosis in north-west India.

A total of 100 patients were enrolled in this study with the clinical diagnosis of multiple sclerosis (MS). This included prospective analysis of 35 patients and retrospective analysis of 65 patients from their medical records spanning a period from January 1986 to March 1998. They were divided into 3 groups (i) overall group (ii) MRI group (where MRI was available) (iii) No MRI group (where MRI was not available). Data in terms of clinical features and laboratory investigations were compared in the three groups. MS was found to constitute 2.54% of neurology admission between January 1993 to December 1997. It was higher as compared to previous data from our institute (1.58%). Cerebellar symptoms were higher in the MRI group as compared to the non MRI group. The clinical spectrum of MS in the MRI group was comparable to that in the west. Obviously the MRI helps in early diagnosis of milder and atypical cases. Oligoclonal bands were found in 30.5% of cases only.

Traumatic dissection of extracranial internal carotid artery and subclavian artery.

A case of a young, adult male presenting with acute post-traumatic dissection involving the left internal carotid and subclavian artery is described.

Unusual manifestations of thalamic strokes.

Four patients of thalamic strokes with different symptoms are reported. The first had thalamic haemorrhage and developed delayed blepharospasm. The second patient had occlusion of posterior cerebral artery causing infarction of lateral thalamus and occipital lobes. The remaining two patients exhibited ipsilateral hemisensory loss and hemiataxia in absence of hemiparesis (thalamic ataxia). Both had circumscribed lesions in lateral thalamus. 'Thalamic ataxia' has a distinct localizing value. Thalamic strokes produce heterogenous clinical manifestations attributed to the involvement of different nuclei.

Comparison of cellular responses in single- and multiple-lesion neurocysticercosis.

Leucocytes from 14 cases of neurocysticercosis who had multiple lesions showed a significantly lower level of chemotaxis than those from healthy controls [with mean (S.D.) movements of 49.86 (15.0) and 89.1 (12.9) microns, respectively; P < 0.05). In contrast, the leucocytes from 14 cases with single lesions had similar chemotactic responses to the controls. Although the level of lymphoproliferation stimulated with phytohaemagglutinin, a measure of T-lymphocyte function, was also considerably less using cells from the multiple-lesion cases than when cells from the single-lesion cases were used, the difference was not statistically significant [0.644 (0.248) of control values v. 0.463 (0.317); P < 0.1]. Flow cytometry indicated that the total numbers of CD4 cells and CD4/CD8 ratios in all blood samples were normal. It therefore appears that, among neurocysticercosis patients, only those with multiple lesions have defective neutrophils and may also have dysfunctional lymphocytes.

Cerebellar degeneration following neuroleptic malignant syndrome.

A 55-year-old woman with a history of bipolar affective disorder developed hyperpyrexia, rigidity and depressed consciousness (neuroleptic malignant syndrome) after commencing neuroleptic therapy. On regaining consciousness, she was mute and had signs suggesting pancerebellar involvement. Hyperpyrexia, which is a cardinal feature of neuroleptic malignant syndrome, may have caused cerebellar damage. Neuroleptic malignant syndrome needs both early recognition and prompt treatment to obviate devastating complications.