A case of myokymia-cramp syndrome successfully treated with gabapentin

We report a case of "myokymia-cramp syndrome", a rare and benign disease consisting of muscular cramps in the upper and lower limbs associated with generalized myokymias. In our patient, cramps had been present since adolescence and had increased in frequency and duration during the last 3 years, occurring about 8 or 9 times a day. Cramps were mainly nocturnal and also precipitated by walking; a previous treatment with carbamazepine did not improve the symptoms. Gabapentin therapy proved to be very satisfactory in relieving muscular cramps with a relatively low dosage (600 mg/day) and without any remarkable side effects. The possible interpretation of the mechanism involved in gabapentin induced relief of cramps is discussed. Gabapentin should be considered as a safe alternative treatment for muscular cramps.     

Electrophysiological study in patients with chronic hepatic insufficiency

Twenty patients affected by chronic hepatic insufficiency were studied by means of combined EEG, VEP and BAEP recordings. Subjects were classified, according to Parsons-Smith criteria, in grade 0 (without any clinical sign) and grade I (with minimal mental disturbances). In group 0 patients an elevated incidence of VEP alterations (40%) was observed, while EEG and BAEP recordings were less frequently (10%) abnormal. In group I patients a high degree of EEG (60%), VEP (70%) and BAEP (70%) abnormalities was found. Mean latency and interpeak interval values in group I patients were significantly prolonged if compared with the grade 0 and control groups. No correlations were found between electrophysiological data and blood biochemical parameters examined (ammoniemia, aminoacidemic pattern).     

Suboccipital injection with a mixture of rapid- and long-acting steroids in cluster headache: a double-blind placebo-controlled study

Oral steroids can interrupt bouts of cluster headache (CH) attacks, but recurrence is frequent and may lead to steroid-dependency. Suboccipital steroid injection may be an effective 'single shot' alternative, but no placebo-controlled trial is available. The aim of our study was to assess in a double-blind placebo-controlled trial the preventative effect on CH attacks of an ipsilateral steroid injection in the region of the greater occipital nerve. Sixteen episodic (ECH) and seven chronic (CCH) CH outpatients were included. ECH patients were in a new bout since no more than 1 week. After a one-week run-in period, patients were allocated by randomization to the placebo or verum arms and received on the side of attacks a suboccipital injection of a mixture of long- and rapid-acting betamethasone (n=13; Verum-group) or physiological saline (n=10; Plac-group). Acute treatment was allowed at any time, additional preventative therapy if attacks persisted after 1 week. Three investigators performed the injections, while four others, blinded to group allocation, followed the patients. Follow-up visits were after 1 and 4 weeks, whereafter patients were followed routinely. Eleven Verum-group patients (3 CCH) (85%) became attack-free in the first week after the injection compared to none in the Plac-group (P=0.0001). Among them eight remained attack-free for 4 weeks (P=0.0026). Remission lasted between 4 and 26 months in five patients. A single suboccipital steroid injection completely suppresses attacks in more than 80% of CH patients. This effect is maintained for at least 4 weeks in the majority of them.     

Granulocyte colony-stimulating factor promotes the generation of regulatory DC through induction of IL-10 and IFN-alpha

We have recently demonstrated that G-CSF promotes the generation of human T regulatory (T(REG)) type 1 cells. In this study, we investigated whether the immunomodulatory effects of G-CSF might be mediated by DC. CD14(+) monocytes were cultured with serum collected after clinical administration of G-CSF (post-G), which contained high amounts of IL-10 and IFN-alpha. Similar to incompletely matured DC, monocytes nurtured with post-G serum acquired a DC-like morphology, expressed high levels of costimulatory molecules and HLA-DR, and exhibited diminished IL-12p70 release and poor allostimulatory capacity. Importantly, post-G DC-like cells were insensitive to maturation stimuli. As shown by neutralization studies, IFN-alpha and, even more pronounced, IL-10 contained in post-G serum inhibited IL-12p70 release by post-G DC-like cells. Furthermore, phenotypic and functional features of post-G DC-like cells were replicated by culturing post-G monocytes with exogenous IL-10 and IFN-alpha. Post-G DC-like cells promoted Ag-specific hyporesponsiveness in naive allogeneic CD4(+) T cells and orchestrated a T(REG) response that was dependent on secreted TGF-beta 1 and IL-10. Finally, neutralization of IL-10 and IFN-alpha contained in post-G serum translated into abrogation of the regulatory features of post-G DC-like cells. This novel mechanism of immune regulation effected by G-CSF might be therapeutically exploited for tolerance induction in autoimmune disorders.     

Novel SACS mutations in autosomal recessive spastic ataxia of Charlevoix-Saguenay type

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is an early-onset familial disease with prominent myelinated fibers in the optic fundus. ARSACS is frequent in the Charlevoix-Saguenay region of Quebec but rare elsewhere. Mutations in SACS, encoding sacsin, a protein of unknown function, are associated with ARSACS. The authors identified three new SACS mutations in two Italian patients whose phenotype closely matches that of Quebec cases, but without retinal striation.     

Survival and cell cycle control in early hematopoiesis: role of bcl-2, and the cyclin dependent kinase inhibitors P27 and P21

Homeostasis of the hematopoietic system is maintained by proliferation and differentiation of a small number of long-term surviving, self-renewing stem cells, which give rise to the fully mature elements. The fine interplay between differentiation, proliferation and death by apoptosis determines the equilibrium of this system. Thus, genes involved in the control of these processes are very important in the regulation and development of hematopoietic cells especially in the initial stages. The interactions among cyclins, their specific cyclin-dependent kinases (CDKs) and, a number of cyclin-dependent kinase inhibitors (CDKIs) such as p27 and p21, exert a direct control on the cell cycle but can also produce other independent effects on hematopoietic differentiation. Proteins of the Bcl-2 family are also crucial in regulating the balance between entry into apoptosis and survival capacity and their roles change in the course of differentiation. In addition, a number of autocrine and paracrine soluble factors (such as TGF-beta1) modulate the behavior and differentiation potential of hematopoietic elements. Studies on a few in vitro systems of early hematopoietic differentiation have stressed the importance of Bcl-2 and of the CDKIs p27 and p21 at this stage, have confirmed cell-cycle independent effects and have demonstrated how the modulation and the effects in response to different stimuli is mostly dependent on the differentiation stage of the target cells.     

Transplantation of autologous peripheral blood progenitor cells: impact of CD34-cell selection on immunological reconstitution

Peripheral blood progenitor cells (PBPC) represent an ideal source of stem cells for autologous transplantation because of technical advantages and more favourable engraftment kinetics. The reconstituion of a functional immune system occurs earlier in patients transplanted with cytokine-mobilized autologous PBPC compared with bone marrow; because of the greater T-cell content in PBPC products, donor-derived antigen-specific T-cells transferred with the graft might contribute to short-term immunity in transplant recipients. Despite a prompt reconstitution of B- and T-cell numbers, both B- and T-cell function are profoundly impaired for a prolonged period of time after PBPC infusion. The positive selection of CD34+ cells might provide effective tumor cell purging without compromising hematopoietic recovery in patients with acute leukemia, multiple myeloma, breast cancer and non-Hodgkin's lymphoma, whose autografts have been reported to contain malignant cells which might promote disease relapse. However, the incidence of viral infections in the early posttransplant period might be increased after CD34-selected compared with unmanipulated PBPC transplants, as a result of the lack of accessory and immune cells in the graft. The purpose of this review is to provide an update on immunological reconstitution after transplantation of autologous PBPC; in particular, emphasis will be placed on the mechanisms of immune dysfunction after the infusion of unmanipulated and CD34-selected autografts.