Neuropsychiatric systemic lupus erythematosus: a diagnostic challenge

A 58-year-old woman presented to neuropsychiatric services with increased frequency of confusional episodes and intermittent psychotic symptoms. She had a 19-year history of atypical epileptic seizures and cognitive decline. Detailed review of history and clinical investigations revealed that she had accumulated sufficient features to meet diagnostic criteria for systemic lupus erythematosus (SLE). She had previously had lymphopenia and a malar rash; she had positive antinuclear, anti-Ro (anti-Sjögren's-syndrome-related antigen A) and anti-SM (anti-Smith Antibody) antibodies, and elevated erythrocyte sedimentation rate. The seizures, cognitive impairment and psychosis were attributable to neuropsychiatric SLE. Treatment with immune-modulating therapy, cyclophosphamide, resulted in significant improvement in subjective and objective clinical presentation. Neuropsychiatric SLE should be considered a potential differential diagnosis for patients presenting with seizures, psychotic symptoms or cognitive decline. A detailed clinical evaluation with review of the medical history and appropriate laboratory analyses allows this diagnosis to be made, and appropriate treatment to be initiated

POEMS neuropathy: optimising diagnosis and management

POEMS syndrome is a rare and disabling autoinflammatory condition characterised by a typical peripheral neuropathy and the presence of a monoclonal plasma cell disorder. The acronym 'POEMS' represents the complex and multisystem features of the disease, including polyneuropathy, organomegaly, endocrinopathy, a monoclonal plasma cell disorder and skin disease. The diagnosis of POEMS is a significant challenge because of the heterogeneity of clinical presentations and variation of POEMS features. Patients are often misdiagnosed with another cause of inflammatory neuropathy and receive one or more ineffective immunomodulatory medications, resulting in delayed diagnosis and further clinical deterioration before a diagnosis is made. University College London Hospitals sees one of the largest reported POEMS cohorts in Europe, and runs a multispecialist clinic to assist with diagnosis, treatment and ongoing support. This review draws upon our experience to present the typical features of POEMS syndrome and highlight diagnostic conundrums commonly experienced, supplemented with clinical cases. We provide an investigative guide for clinicians when considering POEMS as the diagnosis, and propose a treatment algorithm that centres on the site and degree of monoclonal cell proliferation

Diagnosis of amyloid neuropathy

Systemic amyloidosis can be hereditary or acquired. The autosomal dominant hereditary transthyretin amyloidosis and the acquired light-chain amyloidosis, the result of a plasma cell dyscrasia, are multisystem disorders with cardiovascular, autonomic and peripheral nerve involvement. There are numerous investigational modalities available to diagnose systemic amyloidosis and to assess the extent of organ involvement, but it is frequently misdiagnosed due to its heterogeneous clinical presentations and misleading investigation findings. An accurate and timely diagnosis of amyloid neuropathy can greatly impact on the outcomes for patients, especially as there will soon be new gene-silencing treatments for hereditary transthyretin amyloidosis

Frequent central nervous system, pachymeningeal and plexus MRI changes in POEMS syndrome

OBJECTIVE: Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, skin changes (POEMS) syndrome is a rare multisystem disease associated with a plasma-cell dyscrasia. Although pachymeningeal involvement has occasionally been described, MRI of the central nervous system (CNS) has not yet been extensively investigated. METHODS: We retrospectively evaluated CNS MRI in Europe’s largest single-center cohort of POEMS syndrome. Of 77 patients who have been formally diagnosed with POEMS, 41 had MRI brain and 29 had MRI spine. A control group of 33 patients with chronic inflammatory demyelinating polyneuropathy (CIDP) was used as this is the major differential diagnosis. Of these CIDP patients, 12 underwent both MRI brain and spine, 7 had solely MRI brain and 14 had MRI spine. RESULTS: In 41 POEMS patients with MRI brain, we identified frequent smooth, diffuse meningeal thickening of the cerebral convexities and falx (n = 29, 71%), of which 4 had meningeal collections. 17 (41%) had vascular abnormalities including white-matter disease, of which 4 had established infarcts. Of 29 patients with MRI spine, 17 (59%) had thickening of the brachial and lumbosacral plexus. Conversely in 19 CIDP patients with MRI brain, none had meningeal thickening (p < 0.0001); however, 8 (42%) had vascular abnormalities (p = 0.85). Of 26 patients with MRI spine, 9 (35%) had brachial or lumbosacral plexus thickening (p = 0.06). CONCLUSIONS: In contrast to CIDP, POEMS patients frequently have pachymeningeal thickening. Vascular abnormalities and plexus thickening were also common but not statistically different to CIDP

A diagnostic conundrum

A 26-year-old man was referred with facial weakness, dysarthria, dysphagia, ophthalmoparesis and severely weak and wasted legs. His symptoms had begun when aged 20 with electric shock pains and paraesthesia in both feet progressing over 6 months to the lower calves. He then developed buttock numbness and occasional faecal incontinence. By age 22, he had diffuse lower limb weakness and wasting, with difficulty standing from a seated position and frequent tripping. He became wheelchair-dependent within 3 years

The predictive value of T-tau and AB1-42 levels in idiopathic normal pressure hydrocephalus

BACKGROUND: Idiopathic normal pressure hydrocephalus (INPH) has no reliable biomarker to assist in the selection of patients who could benefit from ventriculo-peritoneal (VP) shunt insertion. The neurodegenerative markers T-tau and Aβ1-42 have been found to successfully differentiate between Alzheimer’s disease (AD) and INPH and therefore are candidate biomarkers for prognosis and shunt response in INPH. The aim of this study was to test the predictive value of cerebrospinal fluid (CSF) T-tau and Aβ1-42 for shunt responsiveness. In particular, we pay attention to the subset of INPH patients with raised T-tau, who are often expected to be poor surgical candidates. METHODS: Single-centre retrospective analysis of probable INPH patients with CSF samples collected from 2006 to 2016. Index test: CSF levels of T-tau and Aβ1-42. Reference standard: postoperative outcome. ROC analysis assessed the predictive value. RESULTS: A total of 144 CSF samples from INPH patients were analysed. Lumbar T-tau was a good predictor of post-operative mobility (AUROC 0.80). The majority of patients with a co-existing neurodegenerative disease responded well, including those with high T-tau levels. CONCLUSION: INPH patients tended to exhibit low levels of CSF T-tau, and this can be a good predictor outcome. However levels are highly variable between individuals. Raised T-tau and being shunt-responsive are not mutually exclusive, and such patients ought not necessarily be excluded from having a VP shunt. A combined panel of markers may be a more specific method for aiding selection of patients for VP shunt insertion. This is the most comprehensive presentation of CSF samples from INPH patients to date, thus providing further reference values to the current literature

Electrodiagnostic subtyping in Guillain–Barr\ue9 syndrome patients in the International Guillain–Barr\ue9 Outcome Study

\ua9 2024 The Authors. European Journal of Neurology published by John Wiley &amp; Sons Ltd on behalf of European Academy of Neurology.Background and purpose: Various electrodiagnostic criteria have been developed in Guillain–Barr\ue9 syndrome (GBS). Their performance in a broad representation of GBS patients has not been evaluated. Motor conduction data from the International GBS Outcome Study (IGOS) cohort were used to compare two widely used criterion sets and relate these to diagnostic amyotrophic lateral sclerosis criteria. Methods: From the first 1500 patients in IGOS, nerve conduction studies from 1137 (75.8%) were available for the current study. These patients were classified according to nerve conduction studies criteria proposed by Hadden and Rajabally. Results: Of the 1137 studies, 68.3% (N = 777) were classified identically according to criteria by Hadden and Rajabally: 111 (9.8%) axonal, 366 (32.2%) demyelinating, 195 (17.2%) equivocal, 35 (3.1%) inexcitable and 70 (6.2%) normal. Thus, 360 studies (31.7%) were classified differently. The areas of differences were as follows: 155 studies (13.6%) classified as demyelinating by Hadden and axonal by Rajabally; 122 studies (10.7%) classified as demyelinating by Hadden and equivocal by Rajabally; and 75 studies (6.6%) classified as equivocal by Hadden and axonal by Rajabally. Due to more strictly defined cutoffs fewer patients fulfilled demyelinating criteria by Rajabally than by Hadden, making more patients eligible for axonal or equivocal classification by Rajabally. In 234 (68.6%) axonal studies by Rajabally the revised El Escorial (amyotrophic lateral sclerosis) criteria were fulfilled; in axonal cases by Hadden this was 1.8%. Conclusions and discussion: This study shows that electrodiagnosis in GBS is dependent on the criterion set utilized, both of which are based on expert opinion. Reappraisal of electrodiagnostic subtyping in GBS is warranted

Immunotherapy for IgM anti-myelin-associated glycoprotein paraprotein-associated peripheral neuropathies

Background Serum monoclonal anti-myelin associated glycoprotein antibodies may be pathogenic in some people with IgM paraprotein and demyelinating neuropathy. Immunotherapies aimed at reducing the level of these antibodies might be expected to be beneficial. Objectives To examine the efficacy of any formof immunotherapy in reducing disability and impairment resulting fromIgManti-myelin associated glycoprotein paraprotein-associated demyelinating peripheral neuropathy. Search strategy We searched the Cochrane Neuromuscular Disease Group Register (March 2005), MEDLINE (January 1966 to March 2005) and EMBASE (January 1980 to March 2005) for controlled trials. We also checked bibliographies and contacted authors and experts in the field. Selection criteria We included randomised or quasi-randomised controlled trials of participants of any age treated with any type of immunotherapy for anti-myelin-associated glycoprotein antibody associated demyelinating peripheral neuropathy with monoclonal gammopathy of undetermined significance of any severity.Our primary outcome measure was change in theNeuropathy Impairment Scale orModified Rankin Scale at six months after randomisation Secondary outcome measures were: Neuropathy Impairment Scale or the Modified Rankin Score at 12 months after randomisation; ten-metre walk time, subjective clinical scores and electrophysiological parameters at six and 12 months after randomisation; IgM paraprotein levels and anti-myelin associated glycoprotein antibody titres at six months after randomisation and adverse effects of treatments. Data collection and analysis We identified eight possible trials. Of these, five randomised controlled trials were included after discussion between the authors. One author extracted and the other checked the data. No missing data could be obtained from trial authors. Main results The five eligible trials (97 participants) tested intravenous immunoglobulin, interferon-alpha or plasma exchange. Only two, of intravenous immunoglobulin, had comparable interventions and outcomes but both were short-term. There were no significant benefits of the treatments used in the outcomes predefined for this review, but not all the predefined outcomes were used in every included trial. Intravenous immunoglobulin showed benefits in terms of improvement in Modified Rankin Scale at two weeks and 10-metre walk time at four weeks. Serious adverse effects of intravenous immunoglobulin are known to occur from observational studies but none were encountered in these trials. Authors\u2019 conclusions There is inadequate reliable evidence from trials of immunotherapies in anti-myelin associated glycoprotein paraproteinaemic neuropathy to recommend any particular immunotherapy treatment. Intravenous immunoglobulin is relatively safe and may produce some short-term benefit. Large well-designed randomised trials of at least six to 12 months duration are required to assess existing or novel therapies