Roberto Cavallo

Carbamazepine Toxicity and Poisoning

SummaryCarbamazepine is the drug of first choice in the treatment of simple and complex partial seizures and trigeminal and glossopharyngeal neuralgias. It is usually preferred to phenobarbitone or phenytoin because of its powerful antiepileptic activity combined with a relative lack of adverse effects. In this article the mechanisms of action and pharmacological properties of carbamazepine are outlined in order to explain the pathogenesis of most side and toxic effects. Most of these effects, namely those affecting the nervous or cardiovascular systems, correlate well with an increased concentration of the drug in plasma and disappear spontaneously upon discontinuation of therapy. Other, less frequent toxic effects, namely aplastic anaemia or fatal hepatitis, may be ascribed to unforeseeable idiosyncratic reactions. Carbamazepine poisoning, usually accidental and sometimes secondary to the coadministration of other drugs, yields a clinical picture with neurological and cardiovascular signs. The outcome is usually favourable, sometimes with spontaneous improvement, and death is a distinct rarity. No specific antidotes are available. The oral administration of activated charcoal has been shown to be an effective therapeutic measure, significantly reducing the plasma half-life of the drug.

Anti-neuronal antibodies in patients with HCV-related mixed cryoglobulinemia

Mixed cryoglobulinemia (MC) is an immunological disorder characterized by immune-complex-mediated systemic vasculitis involving small vessels, which may present with renal, cutaneous, rheumatologic, and/or neurological manifestations. Until recently, the possible appearance of anti-neuronal autoantibodies in peripheral neuropathy occurring in the context of hepatitis C virus (HCV)-associated IgMk/IgG MC has not been extensively addressed. Therefore, a sample of these patients were evaluated by means of immuno-enzyme methods of anti-neuronal autoantibody detection. A significant increase in plasma titers of both anti-GM1 ganglioside and anti-sulfatide was observed. Abnormal titers were associated with evidence of active neuropathy as assessed by electrophysiologic studies. While peripheral neuropathy was traditionally thought to result from axonal ischemic damage caused by deposits of cryoprecipitable immune complexes in the vasa nervorum, a significant association between anti-GM1 and anti-sulfatide antibodies and involvement of the peripheral nervous system was observed in HCV-associated mixed IgMk/IgG cryoglobulinemia. Anti-neuronal reactivity could be a direct trigger of neurologic injury in this disorder.

CD8+ high CD11b+ low T cells (T suppressor-effectors) in multiple sclerosis cerebrospinal fluid are increased during high dose corticosteroid treatment

Using simultaneous dual direct immunofluorescence the effect of high dose intravenous methylprednisolone on the expression of T lymphocyte differentiation antigens in paired cerebrospinal fluid and peripheral blood samples of nine clinically active patients with multiple sclerosis was studied. Corticosteroid treatment was associated with a clinical improvement in eight out of the nine patients. In cerebrospinal fluid of all patients the treatment was associated with a decrease of CD3+, CD4+ and CD8+ T cells, and of intra-central nervous system IgG synthesis. CD8+ high CD11b+ low suppressor-effector T cells behaved differently in the eight patients who improved with treatment, where they significantly increased, and in the patient without clinical response, where they were almost unchanged. Similar phenotypic changes were found in peripheral blood, and all changes returned towards baseline after treatment. The lower sensitivity to corticosteroids of CD8+ high CD11b+ low T cells could change the balance between immunoregulatory T subsets. In this study the increased availability of a subpopulation mainly composed of T cells with a suppressor-effector function was associated with a clinical response to treatment.

High-titer Anti-aquaporin-4-IgG-associated Myelitis in Rhupus Syndrome.

To the Editor: Severe organ damage, especially central nervous system (CNS) involvement, has rarely been reported in patients with rhupus syndrome (RS). Two recent articles in The Journal of Rheumatology 1,2 have discussed this condition, which is a challenge in rheumatology. A 51-year-old woman was referred to our center for longstanding polyarthralgia, fever, malaise, and malar rash associated with a history of neurological abnormalities. In 1999 the patient felt a sudden pain in her back between the shoulder blades and then developed weakness of the upper extremities and paresthesias at the lower ones. No urinary symptoms were found. During the physical examination a decrease of arm strength was recorded, and a loss of sense of touch and of pain from the nipples through the feet. Scans of T2-weighted sequences of magnetic resonance imaging (MRI) of the spine showed a hyperintense lesion involving the medulla from level C5 to T7. An MRI scan of the brain was normal. Examination of the cerebrospinal fluid showed a high protein content and pleocytosis. … Address correspondence to Dr. S. Sciascia, CMID, Struttura Complessa a Direzione Universitaria di Immunologia Clinica, Ospedale Torino Nord Emergenza San G. Bosco ed Universita di Torino, Piazza del Donatore di Sangue 3, 10154 Turin, Italy. E-mail: savino.sciascia{at}unito.it

Neurological Involvement in Sjögren’s Syndrome

Sjogren’s syndrome (SS) is a systemic autoimmune disease mainly characterized by xerophthalmia and xerostomia.