Neural stem cells derived from primitive mesenchymal stem cells reversed disease symptoms and promoted neurogenesis in an experimental autoimmune encephalomyelitis mouse model of multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is an autoimmune inflammatory disease of the central nervous system (CNS). MS affects millions of people and causes a great economic and societal burden. There is no cure for MS. We used a novel approach to investigate the therapeutic potential of neural stem cells (NSCs) derived from human primitive mesenchymal stem cells (MSCs) in an experimental autoimmune encephalomyelitis (EAE) mouse model of MS. METHODS: MSCs were differentiated into NSCs, labeled with PKH26, and injected into the tail vein of EAE mice. Neurobehavioral changes in the mice assessed the effect of transplanted cells on the disease process. The animals were sacrificed two weeks following cell transplantation to collect blood, lymphatic, and CNS tissues for analysis. Transplanted cells were tracked in various tissues by flow cytometry. Immune infiltrates were determined and characterized by H&E and immunohistochemical staining, respectively. Levels of immune regulatory cells, Treg and Th17, were analyzed by flow cytometry. Myelination was determined by Luxol fast blue staining and immunostaining. In vivo fate of transplanted cells and expression of inflammation, astrogliosis, myelination, neural, neuroprotection, and neurogenesis markers were investigated by using immunohistochemical and qRT-PCR analysis. RESULTS: MSC-derived NSCs expressed specific neural markers, NESTIN, TUJ1, VIMENTIN, and PAX6. NSCs improved EAE symptoms more than MSCs when transplanted in EAE mice. Post-transplantation analyses also showed homing of MSCs and NSCs into the CNS with concomitant induction of an anti-inflammatory response, resulting in reducing immune infiltrates. NSCs also modulated Treg and Th17 cell levels in EAE mice comparable to healthy controls. Luxol fast blue staining showed significant improvement in myelination in treated mice. Further analysis showed that NSCs upregulated genes involved in myelination and neuroprotection but downregulated inflammatory and astrogliosis genes more significantly than MSCs. Importantly, NSCs differentiated into neural derivatives and promoted neurogenesis, possibly by modulating BDNF and FGF signaling pathways. CONCLUSIONS: NSC transplantation reversed the disease process by inducing an anti-inflammatory response and promoting myelination, neuroprotection, and neurogenesis in EAE disease animals. These promising results provide a basis for clinical studies to treat MS using NSCs derived from primitive MSCs.

Social Anxiety and Obsessive-Compulsive Disorder Are Common Among Persons With Multiple Sclerosis at King Abdulaziz Medical City, Riyadh.

Background Multiple sclerosis (MS) is associated with a physical disability and disturbed psychosocial functioning in young people. Many psychological and psychiatric comorbidities have been reported in MS. Objective To determine the frequency of social anxiety disorder (SAD) and obsessive-compulsive disorder (OCD) among MS patients and their relation to MS severity. Methods A cross-sectional survey was conducted in an adult MS cohort. Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) and Social Phobia Inventory (SPIN) were used to determine the presence and severity of OCD and SAD. The Statistical Package for the Social Sciences (SPSS) version 22 (IBM Corp., Armonk, NY) was used for statistical analysis. The Mann-Whitney U test and logistic regression were used to assess the association of the two diseases with the severity of MS. Results A total of 145 persons with MS (pwMS) were studied. The mean age was 33.5 (±8.5) years; the mean duration of MS was 7.2 (± 5.1) years. The majority (74.1%) were women; 57.3% were married; 63% had a college education; 50% belonged to the higher middle-class socioeconomic strata. Relapsing-remitting multiple sclerosis was the most common type of MS (92.2%). The mean Expanded Disability Status Scale (EDSS) score was 2.24 (±2.19). SAD was reported by 26.9%, and OCD was reported by 31% of the cohort. PwMS with walking difficulty but not wheelchair-bound had a statistically significant increased risk of SAD (p = 0.036). There was no direct association between MS-related disability and OCD. However, pwMS with SAD were more likely to have concomitant OCD (t=4.68, p-value <0.001, 95% CI: 0.47-1.16). Increasing disability was associated with higher chances of developing social anxiety and, in turn, OCD (t=3.39, p-value <0.001, 95% CI: 0.66-2.52). Conclusions Social anxiety and obsessive-compulsive disorders were present in nearly one-third of pwMS. Impaired walking but not wheelchair dependence was associated with social anxiety. PwMS with SAD were more likely to have obsessive-compulsive disorder.

A Prospective Multicenter Study for Assessing MusiQoL Validity among Arabic-Speaking MS Patients Treated with Subcutaneous Interferon ß-1a.

Few studies examine health-related quality of life (HRQoL) in Arabic-speaking multiple sclerosis (MS) patients. However, HRQoL tools such as the Short Form-36 QoL instrument (SF-36) and the Multiple Sclerosis International QoL (MusiQoL) questionnaire have been validated in other languages. The primary objective of this study was to prospectively assess HRQoL using the MusiQoL questionnaire among Arabic-speaking MS patients treated with subcutaneous interferon (sc IFN ß-1a) over 12 months, as part of a prospective, multinational, multicenter cohort study. Patients' clinical parameters and HRQoL were assessed at baseline, 6 months, and 12 months. Changes in MusiQoL total and subdomain scores were compared using a Friedman test. Correlation between MusiQoL total score and Expanded Disability Status Score (EDSS) was also evaluated. In total, 439 patients from four Arabic-speaking countries were included. The mean age was 32.44 (±0.34) years, 71.5% were female, and 63.1% had an education level of university or above. The mean MS duration was 4.13 (±0.12) years, mean age at first attack was 27.35 (±0.26) years, and mean baseline EDSS score was 2.05 (±0.04). MusiQoL total score significantly improved at 6 months; however, this diminished at 12 months (65.67 ± 0.8 at baseline vs. 67.21 ± 0.79 at 6 months and 65.75 ± 0.8 at 12 months; p = 0.0015). Several aspects of patients' HRQoL including activity of daily living, physical well-being, symptoms, and coping improved. Overall HRQoL measured using SF-36 remained generally unchanged over time (p = 0.215). There was a statistically significant inverse relationship between change in EDSS score over time and change in overall MusiQoL score over time. In summary, findings confirm the utility of using MusiQoL for assessing changes in HRQoL during treatment with sc IFN ß-1a in Arabic-speaking patients with MS.

Treatment of Middle East respiratory syndrome with a combination of lopinavir/ritonavir and interferon-ß1b (MIRACLE trial): statistical analysis plan for a recursive two-stage group sequential randomized controlled trial.

The MIRACLE trial (MERS-CoV Infection tReated with A Combination of Lopinavir/ritonavir and intErferon-ß1b) investigates the efficacy of a combination therapy of lopinavir/ritonavir and recombinant interferon-ß1b provided with standard supportive care, compared to placebo provided with standard supportive care, in hospitalized patients with laboratory-confirmed MERS. The MIRACLE trial is designed as a recursive, two-stage, group sequential, multicenter, placebo-controlled, double-blind randomized controlled trial. The aim of this article is to describe the statistical analysis plan for the MIRACLE trial. The primary outcome is 90-day mortality. The primary analysis will follow the intention-to-treat principle. The MIRACLE trial is the first randomized controlled trial for MERS treatment. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02845843. Registered on 27 July 2016.

Exploring the outcome of multiple sclerosis among Saudi adult patients. A single-centered cross-sectional study at King Abdulaziz Medical City in Riyadh, Saudi Arabia.

OBJECTIVE: To assess the outcome and impact of multiple sclerosis (MS) using validated Arabic versions of the Barthel index (BI) multiple sclerosis impact scale (MSIS-29), the modified Rankin scale (mRS), and the expanded disability status scale (EDSS). METHODS: A cross-sectional study conducted at King Abdulaziz Medical City in Riyadh, Kingdom of Saudi Arabia, during July-November 2017. All Saudi adult patients diagnosed with MS between 2000-2016 (269 patients) were included. Patients were contacted via phone calls and were assessed using a newly developed and validated multi-component questionnaire that included demographic data, disease course, and Arabic versions of the scales RESULTS: Out of 269 patients, 210 (78.2%) responded. The average patient age was 37.44+/-10.3 years. The majority were females (69.5%). Only, 51 (24.3%) patients reported worsening conditions. Annually, the average relapse rate was 2.28+/-1.91. In regard to patient outcomes, 120 (57.1%) showed no significant disability in mRS, 146 (69.5%) were ambulatory without aid in EDSS, and 185 (89.4%) were independent in BI scores. The average MSIS-29-PHYS score was 33.6+/-27.6 and MSIS-29-PSYCH score was 38.2+/-25.8. Modified Rankin scale and EDSS were significantly associated with the current use of disease-modifying therapy (DMT). Modified Rankin scale was negatively associated with delayed diagnosis. Barthel index showed significant association with medication compliance and the absence of attacks. CONCLUSION: Majority of patients had a favorable outcome that was linked with the use of DMT, compliance, early diagnosis, and absence of attacks.

Treatment of Middle East Respiratory Syndrome with a combination of lopinavir-ritonavir and interferon-ß1b (MIRACLE trial): study protocol for a randomized controlled trial.

BACKGROUND: It had been more than 5 years since the first case of Middle East Respiratory Syndrome coronavirus infection (MERS-CoV) was recorded, but no specific treatment has been investigated in randomized clinical trials. Results from in vitro and animal studies suggest that a combination of lopinavir/ritonavir and interferon-ß1b (IFN-ß1b) may be effective against MERS-CoV. The aim of this study is to investigate the efficacy of treatment with a combination of lopinavir/ritonavir and recombinant IFN-ß1b provided with standard supportive care, compared to treatment with placebo provided with standard supportive care in patients with laboratory-confirmed MERS requiring hospital admission. METHODS: The protocol is prepared in accordance with the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) guidelines. Hospitalized adult patients with laboratory-confirmed MERS will be enrolled in this recursive, two-stage, group sequential, multicenter, placebo-controlled, double-blind randomized controlled trial. The trial is initially designed to include 2 two-stage components. The first two-stage component is designed to adjust sample size and determine futility stopping, but not efficacy stopping. The second two-stage component is designed to determine efficacy stopping and possibly readjustment of sample size. The primary outcome is 90-day mortality. DISCUSSION: This will be the first randomized controlled trial of a potential treatment for MERS. The study is sponsored by King Abdullah International Medical Research Center, Riyadh, Saudi Arabia. Enrollment for this study began in November 2016, and has enrolled thirteen patients as of Jan 24-2018. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT02845843 . Registered on 27 July 2016.

Erdheim-Chester Disease with No Skeletal Bone Involvement and Massive Weight Loss.

Erdheim-Chester disease (ECD) is a rare type of non-Langerhans cell histiocytosis, with only 550 cases reported worldwide. ECD is characterized by diffuse histiocytic infiltration of multiorgans. The age of presentation of this disease is typically between 40 and 70 years. Bone disease is the most common symptom, as unique radiological findings of long bone sclerosis occur in 96% of cases. Furthermore, BRAF V600E mutation is detected in 60% of ECD cases. In this manuscript, we are describing a unique case of ECD; the patient is younger than most reported cases and has no bone pain or any skeletal involvement. This patient has unintentionally lost about 50% of his body mass and is suffering from progressive cerebellar manifestations with radiological evidence of cerebellar atrophy, in contrast to the usual ECD manifestation of cerebellar infiltration. In addition, the patient has cardiac, retroperitoneal, and perinephric involvement, but he retains his sexual drive and fertility. A tissue biopsy from the retroperitoneal mass displayed typical morphological and immunohistochemical features of ECD, and BRAF V600E mutation was detected. He was treated with pegylated interferon alpha, but his disease progressed and the treatment was changed to vemurafenib to which he had an excellent response at 6 weeks.

Uncommon Presentation of Idiopathic Intracranial Hypertension in a Patient with Polycystic Ovary Syndrome: A Case Report.

INTRODUCTION: Idiopathic intracranial hypertension is a rare condition characterized by increased intracranial pressure without clinical, laboratory, or radiological evidence of intracranial pathology. Early management could prevent irreversible outcomes. CASE PRESENTATION: A 17-year-old single Arabian female of Arab origin presented with a 2-day complaint of horizontal diplopia and transient visual obscurations. She denied any history of headache or decreased vision. The patient was diagnosed with polycystic ovary syndrome a year prior to presentation. Examination revealed bilateral moderate papilledema and limited left eye abduction. However, visual acuity and fields were normal. Increased intracranial pressure was confirmed by lumbar puncture opening pressure (550 mm H₂O). The cerebrospinal fluid composition and imaging of brain and cerebral venous system were normal. The diagnosis of idiopathic intracranial hypertension was confirmed and the patient was treated with acetazolamide 500 mg twice per day. The symptoms totally resolved within 3 days and the papilledema disappeared after 2 months. CONCLUSION: Awareness of such uncommon presentation of idiopathic intracranial hypertension emphasizes the critical importance of detailed ophthalmic examination and shows the good prognosis of early management.

Intravenous Versus Nonintravenous Benzodiazepines for the Cessation of Seizures: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

BACKGROUND: The acquisition of intravenous (IV) access in the actively convulsing patient is difficult. This often delays the administration of the IV benzodiazepine (BDZ) necessary for seizure cessation. Delays in seizure cessation are associated with increased pharmacoresistance, increased risk of neuronal injury, worse patient outcomes, and increased morbidity. OBJECTIVE: The objective was to assess whether the delay imposed by IV access acquisition is justified by improved outcomes. We compared IV versus non-IV BDZ efficacy in the real world with regard to failure rates (primary outcome), interval to seizure control, and observed complications (secondary outcomes). METHODS: A systematic review was performed using Medline, Embase, and the Cochrane Library. All studies published or in press from the inception of the respective database to July 2016 were included. Only randomized and quasi-randomized controlled trials directly comparing IV to non-IV (buccal, rectal, intranasal, or intramuscular) BDZ were included. RESULTS: Our search strategy retrieved 2,604 citations for review. A total of 11 studies were finally included in qualitative synthesis and 10 in quantitative analysis. Only one was of high quality. For treatment failure, non-IV BDZ was superior to IV BDZ (odd ratio [OR] = 0.72; 95% confidence interval [CI] = 0.56-0.92). However, no significant difference was found between the two treatments in the pediatric subgroup (OR = 1.16; 95% CI = 0.74-1.81). Non-IV BDZ was administered faster than IV BDZ and therefore controlled seizures faster (mean difference = 3.41 minutes; 95% CI = 1.69-5.13 minutes) despite a longer interval between drug administration and seizure cessation (mean difference = 0.74 minutes; 95% CI = 0.52-0.95 minutes). Respiratory complications requiring intervention were similar between non-IV BDZ and IV BDZ, regardless of administration route (risk difference = 0.00; 95% CI = -0.02 to 0.01). CONCLUSION: Non-IV BDZ, compared to IV BDZ, terminate seizures faster and have a superior efficacy and side effect profile. Higher-quality studies and further evaluation in different age groups are warranted.

Cultural acceptance of robotic telestroke medicine among patients and healthcare providers in Saudi Arabia. Results of a pilot study.

OBJECTIVE: To determine the degree of satisfaction and acceptance of stroke patients, their relatives, and healthcare providers toward using telestroke technology in Saudi Arabia. METHODS: A cross-sectional study was conducted between October and December 2012 at King Abdulaziz Medical City, Ministry of National Guard Affairs, Riyadh, Saudi Arabia. The Remote Presence Robot (RPR), the RP-7i (FDA- cleared) provided by InTouch Health was used in the study. Patients and their relatives were informed that the physician would appear through a screen on top of a robotic device, as part of their clinical care. Stroke patients admitted through the emergency department, and their relatives, as well as healthcare providers completed a self-administered satisfaction questionnaire following the telestroke consultation sessions. RESULTS: Fifty participants completed the questionnaire. Most subjects agreed that the remote consultant interview was useful and that the audiovisual component of the intervention was of high quality; 98% agreed that they did not feel shy or embarrassed during the remote interview, were able to understand the instruction of the consultant, and recommended its use in stroke management. Furthermore, 92% agreed or strongly agreed that the use of this technology can efficiently replace the physical presence of a neurologist. CONCLUSION: Results suggest that the use of telestroke medicine is culturally acceptable among stroke patients and their families in Saudi Arabia and favorably received by healthcare providers.

Neurophobia among medical students.

OBJECTIVE: To assess the attitude of medical students and junior physicians toward neurology. METHODS: A self-administered, previously validated, questionnaire was distributed among 422 students and junior physicians at King Abdulaziz University, Jeddah, Saudi Arabia from September to December 2012. In this cross-sectional study, the questionnaire included demographic data and 12 statements to examine attitudes toward neurology using a Likert scale. RESULTS: The response rate among participants was 70.3%. The mean age was 22.35 (SD+/-1.28) years. Males comprised 46.2%. While 31.3% of students had not decided regarding their future career, 11.8% selected neurology as their first possible choice. Whereas 29.6% of students were not satisfied with their neurology teaching experience, 84.4% found neurology difficult, and 42.7% of the whole group thought that their neuroscience knowledge was insufficient. Advanced clinical year students (namely, interns) were less likely to consider neurology as a career choice (p=0.001). CONCLUSION: Most of the students had an unfavorable attitude toward neurology on the Likert scale. New strategies are needed to change students` attitude toward this demanding specialty.

The impact of `admit no bed` and long boarding times in the emergency department on stroke outcome.

OBJECTIVES: To examine and test the possible association between boarding time and stroke patients` outcome. METHODS: This study is a retrospective review of stroke patients presenting to the Emergency Department (ED) of King Abdulaziz Medical City, Riyadh, Kingdom of Saudi Arabia from 2007-2010. We excluded thrombolysis cases and those deemed critically ill. We collected time of stroke onset, ED arrival, decision to admit, and arrival to ward. Boarding time (BT) was defined as time of arrival to ward minus time of decision to admit. Primary outcome (PO) was defined as a composite of mortality, and/or any of post-stroke complications. RESULTS: We included 300 patients with a mean age +/- standard deviation of 69 +/- 12 years, and 66.3% were men. The PO occurred in 37.7%. There was no association between BT and PO (odds ratio [OR]=0.9, p=0.3), or any of the secondary outcomes, such as, death (OR=0.97, p=0.5), severe disability (OR=0.97, p=0.3), pneumonia (OR=1, p=0.9), urinary tract infection (OR=1, p=0.9), or neurological deterioration (OR=0.8, p=0.1). Multivariate analysis included gender, age, stroke severity, subtype, hypertension, diabetes, coronary disease, atrial fibrillation, heart failure (HF), onset to ED, BT and ED wait time; only moderate to severe stroke, HF, and previous stroke predicted poor outcome. CONCLUSION: Although `admit no bed` was not associated with adverse effects, the results should be interpreted with caution, and early admission to the stroke unit should be encouraged.

HURT (Headache Under-Response to Treatment) questionnaire in the management of primary headache disorders: reliability, validity and clinical utility of the Arabic version.

BACKGROUND: To support better headache management in primary care, the Global Campaign against Headache developed an 8-question outcome measure, the Headache Under-Response to Treatment (HURT) questionnaire. HURT was designed by an expert consensus group with patient-input. It assesses the need for and response to treatment, and provides guidance on actions to optimize therapy. It has proven content validity.We aim to evaluate the Arabic version of HURT for clinical utility in primary care in Saudi Arabia. METHODS: HURT was translated according to the Global Campaign's translation protocol. We assessed test-retest reliability in consecutive patients of four primary-care centres, who completed HURT at two visits 4-6 weeks apart while receiving usual care. We then provided training in headache management to the GPs practising in these centres, which were randomized in pairs to control (standard care) or intervention (care guided by implementation of HURT). We assessed responsiveness of HURT to clinical change by comparing base-line responses to HURT questions 1-6 with those at follow up. We assessed clinical utility by comparing outcomes between control and intervention pairs after 3 months, using locally-developed 5-point verbal-rating scales: the patient-satisfaction scale (PSS) and doctor-satisfaction scale (DSS). RESULTS: For test-retest reliability in 40 patients, intra-class correlation coefficients were 0.66-0.78 for questions 1-4 and 0.90-0.93 for questions 5-7 (all P ≤ 0.001). For the dichotomous response to question 8, Kappa coefficient=1 (P<0.0001). Internal consistency was good (Cronbach's alpha=0.74). In 342 patients, HURT signalled clinical improvement over 3 months through statistically significant changes in responses to questions 1-6. PSS scores were higher among those in whom HURT recorded improvement, and also higher among those with less severe headache at baseline. Patients treated with guidance from HURT (n=207) were more satisfied than controls (n=135), but this did not quite reach statistical significance (P=0.06). CONCLUSION: The Arabic HURT Questionnaire is reliable and responsive to clinical change in Arabic-speaking headache patients in primary care. HURT showed clinical utility in this first assessment, conducted in parallel with studies elsewhere in other languages, but this needs further study. Other Arabic instruments are not available as standards for comparison.

Status epilepticus and cardiopulmonary arrest in a patient with carbon monoxide poisoning with full recovery after using a neuroprotective strategy: a case report.

INTRODUCTION: Carbon monoxide poisoning can be associated with life-threatening complications, including significant and disabling cardiovascular and neurological sequelae. CASE PRESENTATION: We report a case of carbon monoxide poisoning in a 25-year-old Saudi woman who presented to our facility with status epilepticus and cardiopulmonary arrest. Her carboxyhemoglobin level was 21.4 percent. She made a full recovery after we utilized a neuroprotective strategy and normobaric oxygen therapy, with no delayed neurological sequelae. CONCLUSIONS: Brain protective modalities are very important for the treatment of complicated cases of carbon monoxide poisoning when they present with neurological toxicities or cardiac arrest. They can be adjunctive to normobaric oxygen therapy when the use of hyperbaric oxygen is not feasible.

Granulomatous myositis associated with brucellosis: a case report and literature review.

Brucellosis, a multisystem infectious disorder, continues to be a serious public health problem in some parts of the world. Neurobrucellosis constitutes about 4% of all brucellosis cases. Brucellosis-associated myositis is extremely rare, and there is only 1 reported case in the English literature. We report a 16-year-old boy with subacute, fluctuating, progressive muscle pain, with tenderness, swelling, and diffuse, asymmetric weakness. He also had significantly elevated serum Brucella titers and a muscle biopsy showed inflammatory granulomatous myositis. We review the literature on myositis associated with brucellosis.

The status of acute stroke care in Saudi Arabia: an urgent call for action!

Stroke care in Saudi Arabia lags behind developed countries with only one active stroke centre and seven centres providing thrombolysis out of >350 hospitals nationally; only two hospitals have a stroke team with implemented triaging pathways and beeper system. Via phone interview, we approached 83 neurologists and asked their opinion on stroke care practiced in Saudi Arabia. The study was approved by IRB. There are >350 hospitals in Saudi Arabia and only one centre has a stroke unit, and only seven provide thrombolysis. It is estimated that the number of cases treated with thrombolysis is 50/year for 24 million people. Overall, the neurologists identified their priorities for improving care as: establishing stroke units; increase public awareness; and training health care providers and collaboration. The neurologists we interviewed view acute stroke care in Saudi Arabia as inadequate. This is an urgent call for actions to start organising nation-wide stroke care to close the existing huge evidence-practice gap.

Infection related cerebral venous thrombosis.

The incidence of cerebral venous thrombosis (CVT) has dropped dramatically in recent years. In the past, before the introduction of antibiotics, infection was the main cause of CVT. But this is no longer true. Recently, the occurance of septic CVT is rare, which leads to an increased chance of misdiagnosis and treatment delay. Early suspicion and recognition is very crucial to improve mortality and morbidity rates of this potentially fatal disease. Intravenous, wide spectrum, antibiotics and early surgical drainage of the primary site of infection whenever possible are essential. Anticoagulation with intravenous heparin infusion and corticosteroids use are of uncertain benefit, although some reports have shown some favorable response.

Primary lateral sclerosis: clinical and laboratory features in 25 patients.

OBJECTIVE: : The objective of this study was to characterize the clinical features and natural history of primary lateral sclerosis (PLS). BACKGROUND: : PLS is a motor neuron disorder defined by corticospinal and corticobulbar tract dysfunction without clinically significant lower motor neuron involvement. METHODS: : We collected data from 25 patients with PLS seen in 2 academic neurology departments over a 5-year period. RESULTS: : The PLS population represented approximately 3% of acquired motor neuron disease cases seen during that period. Twenty-three patients (92%) presented with lower limb weakness, spasticity, or difficulty with ambulation. None presented with upper limb symptoms. Eleven patients (44%) developed bulbar symptoms. All patients had hyperreflexia and increased muscle tone. Muscle weakness was observed in 15 patients (60%) and tended to be mild and asymmetric. Needle electromyography (EMG) was normal or showed only fasciculations in 15 patients (60%); 10 patients had features of mild active denervation, consisting of fibrillation or positive sharp wave potentials, but the extent of these findings did not satisfy World Federation of Neurology electrophysiological criteria for the diagnosis of amyotrophic lateral sclerosis. Fourteen patients (52%) continued independent ambulation. Of the 10 patients with active denervation on EMG, 6 (60%) required a walker, scooter, or wheelchair at a mean follow up of 6.2 years. There were no fatalities over the 5-year period. CONCLUSIONS: : Our experience supports the observation that PLS progresses more slowly than other forms of acquired motor neuron disease, particularly amyotrophic lateral sclerosis. Follow-up data suggest that patients with active denervation changes develop greater disability.

Neuromuscular paralysis in the intensive care unit.

OBJECTIVE: To determine the features, causes, risk factors and outcome of acquired neuromuscular paralysis in critically ill patients. METHODS: Retrospective review of all confirmed cases of acquired polyneuropathy and myopathy examined by our Neurology service in the Intensive Care Unit (ICU), at King Fahad National Guard Hospital, Riyadh, Kingdom of Saudi Arabia over a period of 5 years. All patients had comprehensive electrophysiological studies and one third had muscle and nerve biopsies. RESULTS: Thirty cases were included, 8 cases of polyneuropathy, 15 cases of myopathy and 7 cases of mixed neuropathy and myopathy. Absent deep tendon reflexes and absent sensory potential on nerve conduction studies were significantly suggestive of neuropathy. The level of creatine phosphokinase was not of great diagnostic value. Most polyneuropathy and myopathy cases had passed through a stormy ICU course with sepsis and multiorgan failure. The use of high doses of steroids was more associated with myopathy. Seven patients died in ICU, the others were discharged to the wards after a mean ventilation period of 40 days. One patient became chronic ventilator dependent. CONCLUSION: From this series and available literature, it seems that symptomatic myopathy is more frequent than polyneuropathy and some risk factors are common for both (sepsis and multiorgan failure) while the use of steroids is more associated with ICU myopathy. Treating sepsis and stopping corticosteroids results in the improvement of most of the cases.

Neurological disorders and travel.

Travel is associated with a number of neurological disorders that can be divided into two categories: (1) Neurological infections including encephalitides, neurotuberculosis, neurobrucellosis, cysticercosis and trichinosis. Some of these disorders can be prevented by vaccinations, such as Japanese B encephalitis and rabies, some by the use of insect repellents and some by avoiding raw milk products and undercooked meat. (2) Non-infective neurological disorders, such as acute mountain sickness and high altitude cerebral oedema, problems occurring during air travel such as syncope, seizures, strokes, nerve compression, barotrauma and vertigo, motion sickness and foodborne neurotoxic disorders such as ciguatera, shellfish poisoning and intoxication by cassava. This group of diseases and disorders could be prevented if the traveller knows about them, applies simple physiological rules, takes some specific medications and knows how to avoid intoxications in certain geographical areas. Meningococcal meningitis, malaria and jet lag syndrome are extensively discussed in other articles of this issue. The discussion in this paper will be limited to the other disorders.