Lesson of the month 2: Transient reversible amnesia in multiple sclerosis.

Transient amnestic syndromes are fascinating clinical entities and there are several subtypes. Transient global amnesia (TGA) is characterised by sudden onset of anterograde amnesia with repetitive questioning, lasting less than 24 hours. The pathophysiology of TGA involves the medial temporal lobes and hippocampi. Episodes of TGA are thought to involve venous congestion with Valsalva-like activities, vascular or migrainous mechanisms. In contrast, transient epileptic amnesia manifests as brief and frequent episodes of amnesia due to seizure activity in the temporal lobes. Transient memory disturbances can also be caused by transient ischaemic attack. We describe the first reported case of transient reversible amnesia directly attributable to acute demyelination. This case reminds us that multiple sclerosis relapses may present with acute cognitive impairment rather than the more classical physical symptoms. This is an important learning point in terms of appropriate management and eligibility for disease-modifying drugs.

Chronic autoimmune disease caused by somatic mutation to T-lymphocyte regulatory receptors.

Chronic autoimmune diseases are a common cause of death and disability in the developed world. Despite this, their aetiology is unknown and researchers work without an accepted hypothesis as to how these diseases arise. Chronic autoimmunity could result from spontaneous somatic mutation to an autoreactive T helper lymphocyte, causing impairment of the receptor mechanism by which it communicates with regulatory T-cells. This would result in a dysregulated autoreactive T-cell clone. Current experimental evidence suggests this is at least possible, if not probable, and would explain many of the epidemiological and clinical features of chronic autoimmune diseases.

Anticonvulsant hypersensitivity syndrome presenting as aseptic meningitis.

Anticonvulsant hypersensitivity syndrome (AHS) is a rare, potentially life-threatening drug reaction which usually occurs after exposure to aromatic antiepileptics. AHS secondary to non-aromatic antiepileptics is even more rare and there are only few case reports of AHS presenting as aseptic meningitis. We present the case of a 48-year-old patient who presented with meningism within 3 weeks of adding lamotrigine for control of her juvenile myoclonic epilepsy. When lamotrigine was restarted 2 weeks later she developed similar but more severe symptoms which resolved on stopping lamotrigine. Our patient was subsequently rendered seizure free on levetiracetam which has not so far been linked with this syndrome. It is important to be aware of this life-threatening complication associated with the use of antiepileptics.

Serum autoantibodies to cell surface determinants in multiple sclerosis: a flow cytometric study.

Multiple sclerosis is thought to be an autoimmune, inflammatory, cell-mediated disease. However, there is evidence suggesting that autoantibodies could play a role in the pathogenesis of multiple sclerosis. Many studies have looked for antibodies to candidate antigens such as myelin basic protein or myelin-oligodendrocyte glycoprotein, with inconclusive results. In order to determine whether antibodies to cell surface determinants on oligodendrocyte or neuronal cells were present in multiple sclerosis, we used flow cytometry to detect antibody binding to intact cultured human cell lines, comparing sera from multiple sclerosis patients with sera from patients with other inflammatory CNS diseases. Sera from healthy individuals were used to determine a normal range. Significant surface binding of IgG or IgM antibodies to oligodendrocyte precursor (OPC)-derived cell lines was seen in 50% of multiple sclerosis sera with no significant difference between secondary progressive (SPMS) and relapsing-remitting (RRMS) subgroups. In contrast, binding to a neuronal cell line, SK-N-SH, was seen with 70% of SPMS sera compared with 25% of RRMS sera (P < 0.001). No significant difference in antibody binding between multiple sclerosis sera and control sera was seen when OPCs were differentiated or when the cells were permeabilized to expose intracellular antigens. Results from all nine patients with 'benign' multiple sclerosis were indistinguishable from controls. This study represents a systematic approach to begin to define new antigenic targets in multiple sclerosis and demonstrates that antibodies to accessible antigens on the cell surface of both OPCs and neurons are present in some patients. The results lend support to the possibility that autoantibody-mediated processes are important in a subgroup of multiple sclerosis patients. Identification of the cell surface determinants to which the antibodies bind may shed light on new targets for therapeutic intervention.