Immune cells after prolonged Natalizumab therapy: implications for effectiveness and safety.

BACKGROUND: Previous studies on Natalizumab (NAT) have shown increased circulation of most white blood cells (WBC) in multiple sclerosis (MS) patients shortly after its introduction. AIM: To describe peripheral immune cell phenotypes after more than 2 years of continuous NAT therapy and test for associations with clinical response to therapy. METHODS: Peripheral immune cell subsets were analyzed in 44 NAT-MS patients receiving NAT for over 24 months, and in 22 NAT-free control-MS patients. RESULTS: NAT-MS patients displayed significantly higher numbers of all WBC when compared with controls. B lymphocytes exhibited a more pronounced increase when compared with CD4+, CD8+ and NK T-cells (P = 0.011). CD4/CD8 ratio was significantly decreased in NAT-MS patients (P = 0.018) and showed no correlation with the number of NAT doses. The reduced CD4/CD8 ratio was attributable to the 'EDSS improvement' group only, irrespective of age, sex and disease severity. CONCLUSIONS: The study suggests that there is no desensitization effect after prolonged NAT exposure. A reduced CD4/CD8 ratio was associated with long-term response to therapy; thus, those patients who most benefitted from the drug might be at greater risk for opportunistic infections like progressive multifocal leucoencephalopathy (PML). We provide implications for future research for the CD4/CD8 ratio as a possible contributor to the recently developed risk stratification scheme for PML.

Using vestibular evoked myogenic potentials to localise brainstem lesions. A preliminary report.

BACKGROUND: Vestibular Evoked Myogenic Potentials (VEMPs) are saccular responses to acoustic stimuli. They can be recorded from the sternocleidomastoid muscle ipsilaterally to the stimulated ear. Their reflex arc includes the ipsilateral vestibular nuclei. OBJECTIVE: To determine the usefulness of VEMPs in localising brainstem lesions. METHODS: We used VEMPs, Blink Reflex (BR) and Brainstem Auditory Evoked Responses (BAERs) to evaluate six patients presenting with acute ischaemic or haemorrhagic brainstem lesions, or basilar dolichoectasia. RESULTS: MRI in patient one revealed a dorsolateral medullary infarct on the right. VEMP amplitude was reduced ipsilaterally. The R2 BR component was delayed bilaterally upon stimulation of the affected side. Patients two and three had suffered a left lateral lower pontine infarct and a right lateral lower pontine haemorrhage. In patients four and five, MRA revealed dolichoectasia of the basilar artery exerting pressure on the lower lateral pons. VEMP amplitude was reduced ipsilaterally. Patient six had an ischaemic lesion in the right upper lateral pons. The R1, R2i and R2c BR components were delayed ipsilaterally. BAERs waves IV and V were absent on the right. VEMPs were normal. CONCLUSIONS: VEMPs are affected by lesions of the lateral lower pons and upper medulla. Our results suggest that they may be a useful addition in the localisation of such lesions.

Octreotide: a therapeutic option for idiopathic intracranial hypertension.

PURPOSE: To study the effects of octreotide, a somatostatin analogue, in patients with Idiopathic Intracranial Hypertension (IIH). METHODS: We performed a prospective, open-label study of the effect of Octreotide on 26 patients with symptoms and signs of IIH, investigated by brain MRI and lumbar puncture. Octreotide was administered subcutaneously, at an initial dose of 0.3 mg/day; and was gradually increased until headache was relieved (upper-dose limit: 1 mg/day). Treatment with octreotide at 1 mg/day was administered for a maximum of six to eight months and afterwards the dose was gradually tapered. Patients were followed prospectively every month for three years. CSF opening pressure was measured before the treatment was started and again in the first follow-up examination, on month one. In all follow-up visits the presence of papilledema was evaluated by fundoscopy; visual fields and visual acuity were also examined. RESULTS: Overall 24/26 patients improved significantly (92%). Headache was relieved within days (1-10, median 7 days). Papilledema subsided in all 24 patients, in up to two months (35 to 68, median 45 days). Visual disturbances, initially presenting in 20 of our patients, improved in 18 (90%). The mean reduction in CSF pressure after treatment was 20.72A+/-10.7 cmH2O (range 2 to 48). Patients were followed for three years after cessation of treatment. No recurrence of papilledema, or any other symptoms, has been observed. CONCLUSIONS: Octreotide resulted in a significant and sustained improvement of IIH in our patients. These results suggest that it may be an effective alternative to existing treatments for IIH.

Glutathione-S-transferase T1 and M1 gene polymorphisms in Greek patients with multiple sclerosis: a pilot study.

Oxidative stress has been implicated in the pathogenesis of multiple sclerosis (MS). Glutathione-S-transferases (GSTs) are detoxification enzymes, evolved to protect cells against reactive oxygen metabolites. Both GSTT1 and GSTM1 genes exhibit a homozygous deletion polymorphism (null genotype) leading to abolished enzyme activity. We studied the impact of the GSTT1 and GSTM1 polymorphisms on MS susceptibility in a case-control study of 47 Greek patients and 165 controls. Correlations between genotype, gender and disability status were also investigated. The incidence of both GSTT1 and GSTM1 genotypes did not differ significantly between controls and patients. A significantly increased frequency of GSTM1 null genotype was found amongst female patients (65.5%) as compared with males (33.3%, P =0.04). The results suggest that GSTT1 and GSTM1 have no major pathogenetic role on the MS occurrence, nor any strong modifying effect on the disability status. The higher incidence of GSTM1 null genotype observed in female patients, suggests a possible role of the GSTM1 detoxification pathway in a gender-dependent manner.

Neurophysiological monitoring of brainstem function in a patient with Wallenberg syndrome, using Vestibular Evoked Myogenic Potentials.

PURPOSE: We evaluated the use of Vestibular Evoked Myogenic Potentials (VEMPs) in the assessment of neural function, following medullary lesions. METHODS: A 54-year-old male presented with symptoms and signs typical of right lateral medullary (Wallenberg) syndrome. He underwent brain MRI and three successive neurophysiological investigations, which included VEMPs, Brainstem Auditory Evoked Responses (BAERs) and the blink reflex. RESULTS: VEMPs amplitude on the left (unaffected) side was 256.8 microv in the first investigation and remained approximately equal to that value in the following two ones. Their amplitude on the right (affected) side was 37.9 microv, 154.2 microv and 235.2 microv correspondingly. At the same time vertigo, diplopia and nystagmus gradually improved. Right blink reflex comprised a normal R1, but delayed R2 ipsilateral and R2 contralateral responses, which remained unaltered during the follow-up period. Brain MRI disclosed a right dorsolateral medullary infarct. CONCLUSIONS: VEMPs amplitude progressively increased, parallel to the improvement of vestibular symptoms. The blink reflex evolved differently, while BAERs were not affected. As the three evoked responses are mediated by separate neural circuits, they provide information on different aspects of brainstem function. Thus, VEMPs seem to be a useful method that complements existing ones in the assessment of brainstem lesions.