Diagnosis of delirium: a practical approach.

Delirium is an acute disorder of fluctuating attention and awareness with cardinal features that allow it to be positively distinguished from other causes of an acute confusional state. These features include fluctuations, prominent inattentiveness with other cognitive deficits, a change in awareness and visual hallucinations. We describe a framework for diagnosing delirium, noting the need to consider certain caveats and differential diagnoses. Delirium is a clinical diagnosis where a thorough history and clinical examination are much more helpful diagnostically than any single test or combination of tests.

Training in neurology: lessons learnt.

There is no consensus on how to structure and deliver neurology training. The General Medical Council's annual National Training Survey indicates that the quality of UK neurology training is very variable, but does not explain this variation. We used the survey data to identify the four highest and lowest performing sites for neurology training across the UK. We conducted semistructured interviews with groups of local trainees and, separately, local trainers in an exploratory qualitative study, and identified common themes across a range of aspects of neurology training. Here we present our findings, share case studies from top-performing sites and make recommendations on how best to train a neurologist.

Rheumatoid disease: an unusual cause of relapsing meningoencephalitis.

A 73-year-old man presented with three episodes of dysphasia and disinhibited behaviour, a single seizure and transient ischaemic attack-like events characterised by right arm and/or leg weakness. These episodes were separated by month-long asymptomatic intervals. Medical history included rheumatoid arthritis, which was clinically quiescent on leflunomide.Repeated cerebrospinal fluid examination showed a persistent lymphocytosis with mildly reduced glucose and elevated protein; oligoclonal bands and viral PCR were negative. MRI of the brain was initially normal, but 7 months after initial presentation revealed meningeal enhancement with bifrontal cortical hyperintensities on T2/fluid-attenuated inversion recovery. Brain biopsy demonstrated necrotising granulomatous meningitis with mixed T cell and B cell infiltrates and without evidence of vasculitis or infection. Serum anticyclic citrullinated peptide antibodies were strongly positive.The diagnosis of rheumatoid meningoencephalitis was made on the basis of brain biopsy findings and serological evidence of active rheumatoid disease. Steroids and rituximab therapy were started leading to clinical stabilisation.

Guillain-Barré syndrome with exaggerated pleocytosis and anti-GM1 ganglioside antibodies.

An 81-year-old man presented with fever, confusion and rapidly-progressive flaccid tetraparesis. Clinical presentation and neurophysiology were consistent with a severe axonal polyneuropathy. Anti-GM1 and Campylobacter serology were both positive, consistent with postinfectious axonal-variant Guillain-Barré syndrome (GBS). GBS is characterised by albuminocytological dissociation, where an elevated protein and acellular cerebrospinal fluid are typical. However, in this case, CSF analysis revealed an exaggerated pleocytosis (72 white blood cells (WBC)/mm3). No source of central nervous system infection or inflammation was identified despite thorough investigation. The patient was treated with intravenous immunoglobulin and intensive rehabilitation.Albuminocytological dissociation classically distinguishes GBS from infective causes of flaccid weakness (eg, enteroviruses, flaviviruses and HIV). Diagnostic criteria frequently cite a pleocytosis of <50 WBC/mm3 as required in the diagnosis of GBS. However, this case demonstrates that pleocytosis exceeding this level can occur in the presence of convincing evidence of GBS and without demonstrable neurotropic infection.

Neuronal surface and glutamic acid decarboxylase autoantibodies in Nonparaneoplastic stiff person syndrome.

IMPORTANCE: High titers of autoantibodies to glutamic acid decarboxylase (GAD) are well documented in association with stiff person syndrome (SPS). Glutamic acid decarboxylase is the rate-limiting enzyme in the synthesis of γ-aminobutyric acid (GABA), and impaired function of GABAergic neurons has been implicated in the pathogenesis of SPS. Autoantibodies to GAD might be the causative agent or a disease marker. OBJECTIVE: To investigate the characteristics and potential pathogenicity of GAD autoantibodies in patients with SPS and related disorders. DESIGN: Retrospective cohort study and laboratory investigation. SETTING: Weatherall Institute of Molecular Medicine, University of Oxford. PARTICIPANTS: Twenty-five patients with SPS and related conditions identified from the Neuroimmunology Service. EXPOSURES: Neurological examination, serological characterization and experimental studies. MAIN OUTCOMES AND MEASURES: Characterization of serum GAD antibodies from patients with SPS and evidence for potential pathogenicity. RESULTS: We detected GAD autoantibodies at a very high titer (median, 7500 U/mL) in 19 patients (76%), including all 12 patients with classic SPS. The GAD autoantibodies were high affinity (antibody dissociation constant, 0.06-0.78 nmol) and predominantly IgG1 subclass. The patients' autoantibodies co-localized with GAD on immunohistochemistry and in permeabilized cultured cerebellar GABAergic neurons, as expected, but they also bound to the cell surface of unpermeabilized GABAergic neurons. Adsorption of the highest titer (700 000 U/mL) serum with recombinant GAD indicated that these neuronal surface antibodies were not directed against GAD itself. Although intraperitoneal injection of IgG purified from the 2 available GAD autoantibody­ositive purified IgG preparations did not produce clinical or pathological evidence of disease, SPS and control IgG were detected in specific regions of the mouse central nervous system, particularly around the lateral and fourth ventricles. CONCLUSIONS AND RELEVANCE: Autoantibodies to GAD are associated with antibodies that bind to the surface of GABAergic neurons and that could be pathogenic. Moreover, in mice, human IgG from the periphery gained access to relevant areas in the hippocampus and brainstem. Identification of the target of the non-GAD antibodies and peripheral and intrathecal transfer protocols, combined with adsorption studies, should be used to demonstrate the role of the non-GAD IgG in SPS.

Mirror-image temporal arteriovenous malformations presenting with left cervical internal carotid aneurysm.

We report an unusual case of bilateral mirror-image arteriovenous malformations (AVMs) in association with a large internal carotid aneurysm. The patient, a 45-year-old man, was asymptomatic apart from a lump in his neck. Both AVMs were successfully occluded with embolisation and the patient remains clinically well.