Adam Al-Diwani

Oxford University Hospitals NHS Trust, Oxford, England, United Kingdom

Are you Adam Al-Diwani?

Claim your profile

Publications (3)15.84 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: The recent discovery of several potentially pathogenic autoantibodies has helped identify patients with clinically-distinctive central nervous system diseases that appear to benefit from immunotherapy. The associated autoantibodies are directed against the extracellular domains of cell-surface expressed neuronal or glial proteins such as LGI1, the NMDA-receptor and aquaporin-4. The original descriptions of the associated clinical syndromes were phenotypically well-circumscribed. However, as availability of antibody testing has increased, the range of associated patient phenotypes and demographics has expanded. This, in turn, has led to the recognition of more immunotherapy-responsive syndromes in patients presenting with cognitive and behavioural problems, seizures, movement disorders, psychiatric features, and demyelinating disease. While antibody detection remains diagnostically important, clinical recognition of these distinctive syndromes should ensure early and appropriate immunotherapy administration. We review the emerging paradigm of cell-surface directed antibody-mediated neurological diseases, describe how the associated disease spectrums have broadened since the original descriptions, discuss some of the issues regarding antibody detection and syndrome definitions, and emphasize considerations surrounding immunotherapy administration. As these disorders continue to reach mainstream neurology, and even psychiatry, more cell-surface directed antibodies will be discovered and their possible relevance to other commoner disease presentations should become more clearly defined. ANN NEUROL 2014. © 2014 American Neurological Association.
    Annals of Neurology 06/2014; · 11.19 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: An elderly woman presented with disorganised thinking, unusual behaviour and clustered episodes of speech arrest accompanied by right-sided face and arm twitching. The following investigations were normal: interictal electroencephalography, brain MRI, cerebrospinal fluid viral PCR and cell count and voltage-gated potassium channel-complex, N-methyl-d-aspartate receptor, gamma-aminobutyric acid (B) receptor, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor, glycine receptor, glutamic acid decarboxylase and paraneoplastic antibodies. The syndrome showed partial spontaneous resolution but 1 year later, typical postencephalopathic features persisted including disinhibition and alteration of sleep-wake cycle. The most likely clinical diagnosis was autoimmune encephalitis and the broader differential diagnoses are discussed within the article. This case demonstrates the need to be aware of this under-recognised and potentially treatable entity.
    Case Reports 01/2012; 2012.
  • [Show abstract] [Hide abstract]
    ABSTRACT: The nematode Caenorhabditis elegans is an established model organism for studying neurobiology. UNC-63 is a C. elegans nicotinic acetylcholine receptor (nAChR) α-subunit. It is an essential component of the levamisole-sensitive muscle nAChR (L-nAChR) and therefore plays an important role in cholinergic transmission at the nematode neuromuscular junction. Here, we show that worms with the unc-63(x26) allele, with its αC151Y mutation disrupting the Cys-loop, have deficient muscle function reflected by impaired swimming (thrashing). Single-channel recordings from cultured muscle cells from the mutant strain showed a 100-fold reduced frequency of opening events and shorter channel openings of L-nAChRs compared with those of wild-type worms. Anti-UNC-63 antibody staining in both cultured adult muscle and embryonic cells showed that L-nAChRs were expressed at similar levels in the mutant and wild-type cells, suggesting that the functional changes in the receptor, rather than changes in expression, are the predominant effect of the mutation. The kinetic changes mimic those reported in patients with fast-channel congenital myasthenic syndromes. We show that pyridostigmine bromide and 3,4-diaminopyridine, which are drugs used to treat fast-channel congenital myasthenic syndromes, partially rescued the motility defect seen in unc-63(x26). The C. elegans unc-63(x26) mutant may therefore offer a useful model to assist in the development of therapies for syndromes produced by altered function of human nAChRs.
    Journal of Biological Chemistry 10/2010; 286(4):2550-8. · 4.65 Impact Factor