Association analysis of nitric oxide synthases: NOS1, NOS2A and NOS3 genes, with multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is a chronic inflammatory autoimmune disorder of the central nervous system. AIM: To explore the genetic basis of three nitric oxide synthase (NOS) genes: NOS1, NOS2A and NOS3, with susceptibility to MS. SUBJECTS AND METHODS: A total of 122 MS patients and 118 healthy controls screened for NOS1 (rs2682826, rs41279104), NOS2A (CCTTT)n/(TAAA)n and NOS3 (rs1800783, rs1800779, rs2070744, 27bpVNTR) markers, using TaqMan®SNP Genotyping Assays and fragment analysis were enrolled in this study. QRT-PCR and ELISA were used to analyse the expression of NOS3 mRNA and Nitric Oxide (NO) levels. RESULTS: Two NOS3 markers were associated with susceptibility to MS and early disease development. The NOS3 rs1800779 G-allele (p = 0.04) and GG-genotype (p = 0.02) showed association with susceptibility to MS. Short NOS2 (CCTTT)n (p = 0.03) and short/long repeat (p = 0.04) genotypes also showed associations with MS. These associations were intensified by sub-division of patients into Kuwaiti Arabs and Persians (p < 0.05). The NOS3-27 bp-VNTR a-allele was associated with early MS disease onset ≤26 years (p = 0.04). The NOS3-27 bp-VNTR a/b-genotype resulted in 23% lower NO production and the NOS3-rs1800779 AA-genotype resulted in lower NOS3 expression. Haplotypes obtained from NOS2A and NOS3 showed increased susceptibility to MS. NOS1 showed no significant association with MS. CONCLUSION: This study provides evidence for the association between selected NOS2 and NOS3 markers and MS susceptibility.

Cerebral venous thrombosis in Kuwait. Clinical presentation, risk factors, and management.

OBJECTIVE: To explore the pattern of clinical presentations, risk factors, and the sinuses involved in cases of cerebral venous thrombosis (CVT) treated in a tertiary neurological center in Kuwait. METHODS: A retrospective analysis of cases of CVT treated at Ibn Sina Hospital, Kuwait, from January 2000 to October 2010. The records of 71 patients were retrieved and entered in a database. All patients were evaluated with hypercoagulable work up and relevant neuro-imaging studies. RESULTS: Seventy-one patients were included in our study, with a male to female ratio of 1:1.5. The clinical presentations were: headache (93%), seizures (31%), and focal neurological signs (37%). Over two-thirds (n=30) of female patients had a history of oral contraceptive use. Papilledema with raised intracranial pressure was recorded in 20 patients (28%), ovarian hyper-stimulation syndrome with CVT in one patient, and possible Neuro-Behcet`s in 10% (n=7). The venous sinuses involved were superior sagittal sinus in 59% (n=42), and transverse and straight sinuses in 54% (n=38). Hemorrhagic venous infarctions were seen in 18% (n=13). Fifty percent of patients recovered within 2-4 weeks, 15 patients (21%) recovered within 4-12 weeks, and 15 patients (21%) required intensive care unit care with ventilator support for 1-2 weeks. CONCLUSION: Oral contraceptive use was the primary risk factor in female patients. Early diagnosis and immediate treatment with anticoagulants reduce the morbidity and mortality. Serum D-dimer level is more helpful for early diagnosis with sensitivity of 58%.

Single-fiber electromyography of masseter muscle in myasthenia gravis.

Jitter after axonal microstimulation in the masseter muscle was studied in 30 consecutive patients (12 women) with myasthenia gravis (MG). Patients' mean age was 42.3 (12-75), median disease duration was 3 months (1-72), and onset was ocular (15 cases), oculobulbar (7), bulbar (6), or generalized (2). There were 23 newly-diagnosed patients. Nine cases developed purely ocular MG and 21 cases developed generalized MG. In the latter group, five subjects had a rapidly progressive course and 16 subjects had stable or well-controlled disease (MGFA grade 2-3). Six patients did not have circulating anti-acetylcholine receptor antibodies. Masseter single-fiber electromyography (SFEMG) was abnormal in 6 of 9 ocular MG patients and in all generalized cases (overall sensitivity 27 of 30 cases or 90%; confidence interval 79.3%-100.0% at P = 0.95). Masseter should be considered for SFEMG in diagnosis of MG, especially in cases with bulbar onset.

Low back ache treatment with botulinum neurotoxin type A. Local experience in Kuwait.

OBJECTIVE: To investigate the efficacy, safety and tolerability of paraspinal administration of botulinum neurotoxin type A (BoNT-A) in patients with chronic low back ache (LBA). SUBJECTS AND METHODS: Eight patients with chronic LBA were injected with BoNT-A at three sites on either side of lumbar paraspinal muscles. The patients rated their pain intensity using a visual analogue scale (VAS) from 0 to 10, and our physiotherapist assessed the paraspinal muscle spasm using a functional scale (FS) from 0 to 5. The improvement in both VAS and FS 30, 60 and 90 days after BoNT-A from baseline was analyzed separately using paired t test. The correlation between the muscle spasm (FS) and pain relief (VAS) was analyzed using the Spearman's rank correlation coefficient test. The level of statistical significance was p < 0.05. RESULTS: Five (63%) patients showed a remarkable recovery in VAS and FS, whereas 2 (25%) patients showed improvement only in FS. Statistically significant improvement was achieved in VAS and FS independently 30 days (p < 0.02 and p < 0.02, respectively), 60 days (p < 0.01 and p < 0.001, respectively) and 90 days (p < 0.02 and p < 0.001, respectively) after treatment. Pain relief started early and it was independent of relief of muscle spasm 30 days after treatment (r = 0.685; p > 0.05). CONCLUSION: With this limited study, we have demonstrated that the paraspinal injection of BoNT-A is effective in relieving chronic LBA without producing side effects. The injection is an easy procedure, well tolerated and did not require anesthesia or imaging technique.

Stimulated jitter in the masseter muscle: normative values.

Nineteen healthy volunteers (median age, 25; range, 18-51 years) were enrolled in a study to obtain normative values for stimulated jitter in the masseter muscle. Axonal microstimulation was performed via a monopolar needle electrode introduced in the masseter 2-2.5 cm above the mandibular angle on the line connecting it with the lateral canthus. The recording single-fiber electromyography (SFEMG) electrode was inserted anteriorly in the twitching area of the muscle. The mean consecutive difference (MCD) values for the 426 endplates studied followed a distribution skewed to the left, with a minimum value of 4.3 micros, maximal 44.7 micros, and a maximum of distribution at 11 micros. Mean pooled MCD measured 16.0 micros, and the mean of mean MCD per study was 13.6 micros. The value of the 95th upper percentile for an individual fiber was 29.3 micros. We suggest an upper normal limit for mean MCD per study of 21 micros and upper normal limit of MCD for individual fibers of 30 micros. The stimulated jitter study of masseter muscle is easy and reliable.

Clinical and neurophysiological pattern of Guillain-Barré syndrome in Kuwait.

OBJECTIVE: To study the clinical and neurophysiological pattern of Guillain-Barré syndrome (GBS) in Kuwait. MATERIALS AND METHODS: The clinical records of consecutive GBS patients admitted to Ibn Sina Hospital, Kuwait, during a 7-year period between 1997 and 2003 were analyzed. RESULTS: Of the 41 cases, 77% were male. The majority of the cases presented during the winter months and a preceding infection was reported in two thirds of them. Proximal lower limb (LL) weakness was the predominant clinical presentation. Nerve conduction studies (NCS) demonstrated a demyelinating pattern in 70%, an axonal pattern in 15%, mixed type in 5% and no abnormality in the remaining 5%. The majority of the patients (73%) improved with one course of intravenous immunoglobulin (IV IG). Mean recovery time (MRT) was 4.4 weeks. Delayed recovery (MRT > or =6 weeks) was noted in patients with predominant distal weakness in the LL (MRT 7.8 weeks; p = 0.001), proximal weakness in the upper limb (UL) (MRT 6 weeks; p = 0.005), autonomic disturbance (MRT 6.5 weeks; p = 0.05), and axonal type GBS (MRT 6 weeks; p = 0.001). CONCLUSION: The presence of predominant distal weakness in LL, proximal weakness in UL, autonomic disturbance and axonal pattern in NCS predict a poor outcome. Hence we recommend early immunomodulatory therapy in patients presenting with these features.

Guillain-Barré syndrome in a case of acute lymphoblastic leukaemia. A case report.

OBJECTIVE: To report a case of severe Guillain-Barré syndrome in a 32-year old female patient diagnosed with acute lymphoblastic leukaemia who was on chemotherapy. CLINICAL PRESENTATION AND INTERVENTION: The patient received chemotherapy including vincristine and steroids according to the Medical Research Council United Kingdom Acute Lymphoblastic Leukaemia-12 (MRC UKALL-12) protocol. On the 21st day of the first induction course she developed acute fulminant quadriparesis with total areflexia. The clinical features, nerve conduction and the cerebrospinal fluid studies were consistent with acute Guillain-Barré syndrome. She was treated with a 5-day course of intravenous immunoglobulins (IVIG) that resulted in only partial improvement. A second course of IVIG was given 2 weeks later that improved her condition slowly and steadily over a period of 12-16 weeks; the patient was able to walk with minimal support. CONCLUSION: The fulminant neuropathy was most likely due to the association between Guillain-Barré syndrome and leukaemia rather than vincristine neurotoxicity. IVIG was an effective and non-invasive treatment for Guillain-Barré syndrome associated with the malignancy.

Diagnostic dilemmas in acute intermittent porphyria. A case report.

OBJECTIVE: To present the importance of early diagnosis of acute intermittent porphyria (AIP) in patients with atypical presentation and discuss the diagnostic problems encountered in this case. CLINICAL PRESENTATION: A 15-year-old girl presented with upper respiratory tract infection, fever, seizures and abdominal pain. An initial diagnosis of encephalitis was made. She received antiviral drugs and anticonvulsants. Two weeks later, she developed progressive flaccid quadriplegia and facial weakness. She also developed respiratory paralysis and was intubated. Cytoalbuminous dissociation was seen in the cerebrospinal fluid. A diagnosis of severe Guillain-Barré syndrome was made. INTERVENTION: The patient received a course of intravenous immunoglobulins which did not result in any clinical improvement. Plasmapheresis, started after 12 weeks, led to partial improvement. The patient continued to have attacks of seizures, abdominal pain and vomiting with severe quadriparesis. A repeat screening test for urine porphyrins was positive, and AIP was confirmed by specific porphobilinogen deaminase in the blood. The patient was treated with large doses of intravenous glucose, followed by injections of hematin. The patient improved remarkably. She was extubated, discharged from Intensive Care Unit and started on a rehabilitation program. CONCLUSION: This patient was initially diagnosed erroneously with a negative screening test for AIP and consequently treated inappropriately. The proper diagnosis was made after repeating the screening test followed by specific tests of porphobilinogen deaminase.