Cost-minimisation analysis of plasma exchange versus IVIg in the treatment of autoimmune neurological conditions.

BACKGROUND: Plasma exchange (PLEX) is an effective treatment for antibody-mediated neurological disorders and has been shown to be equally efficacious to intravenous immunoglobulin (IVIg) with comparable adverse event profiles. IVIg has traditionally been the preferred treatment option due to its ease of use. However, advancing technology has allowed PLEX to be performed with a centrifugal system via peripheral access as opposed to central access via a membrane filter. METHODS: We prospectively collected data from a cohort of patients who underwent PLEX at the Wessex Neurological Centre, UK, to perform a cost-minimisation analysis comparing PLEX to IVIg, the standard of care, between May 2019 and May 2020. Data obtained included indication, admission type (inpatient, daycase or intensive care), access (peripheral or central), number of PLEX cycles, exchange volume, patient weight, complications and clinical outcomes. The cost of PLEX delivered in an outpatient setting for an average 80kg person was calculated and compared to the equivalent cost of delivering IVIg by means of a cost-minimization model. RESULTS: The provision of PLEX was roughly half as costly when compared to what it would have been for IVIg (£886 per exchange vs £1778 per infusion or £4432 per cycle of 5 exchanges vs £8890 per cycle of 5 infusions). Our cohort included a total of 44 patients who received a total of 357 PLEX exchanges during the 12-month period (the majority of which were in a daycase setting). We calculated an annual cost saving for PLEX over IVIg of £318,589. The robustness of this result was confirmed by a one-way deterministic sensitivity analysis, showing the cost-effectiveness of PLEX. CONCLUSION: Our findings demonstrate that PLEX is more cost-effective than IVIg in this setting. Our study supports the economic case for development of plasma exchange centres in regional neurology units, a case made all the more relevant in the context of constrained supplies of IVIg.

Diagnosis of pyridoxine-dependent epilepsy in an adult presenting with recurrent status epilepticus.

Pyridoxine-dependent epilepsy (PDE) is a genetic metabolic disease caused by inborn errors affecting vitamin B6 metabolism, which typically presents with neonatal seizures resistant to antiepileptic drugs (AEDs). Treatment with pyridoxine terminates seizures and prevents neurological decline. We describe a case in which the diagnosis was established at the age of 22 years. Birth and development were normal, but there was a history of three isolated tonic-clonic seizures during childhood and adolescence. At the age of 18 years, she developed frequent focal motor seizures, many evolving into tonic-clonic seizures. Electroencephalography identified a focus in the posterior right hemisphere, but magnetic resonance imaging of the brain was normal. Over the next 3 years, she was hospitalized with uncontrolled seizures on six occasions and spent a total of 121 days in intensive care. The seizures proved resistant to 12 different AEDs. Exome sequencing revealed two pathogenic mutations in ALDH7A1. Since starting on pyridoxine 50 mg once daily, she has been seizure-free, all AEDs have been withdrawn, and cognition has improved to premorbid levels. This case illustrates the importance of considering PDE in drug-resistant epilepsy in adults.

Plasma exchange in neurological disease.

Plasma exchange is a highly efficient technique to remove circulating autoantibodies and other humoral factors rapidly from the vascular compartment. It was the first effective acute treatment for peripheral disorders such as Guillain-Barré syndrome and myasthenia gravis before intravenous immunoglobulin became available. The recent recognition of rapidly progressive severe antibody-mediated central nervous system disorders, such as neuromyelitis optica spectrum disorders and anti-N-methyl-D-aspartate-receptor encephalitis, has renewed interest in using plasma exchange for their acute treatment also. In this review we explain the principles and technical aspects of plasma exchange, review its current indications, and discuss the implications for its provision in the UK.

Refractory CIDP with chronic lymphocytic leukaemia responding to chemoimmunotherapy.

Chronic inflammatory demyelinating polyneuropathy (CIDP) has a variable clinical course with 15% remaining refractory to treatment. We report a woman with severe refractory CIDP and coexisting chronic lymphocytic leukaemia (CLL) who improved dramatically after chemoimmunotherapy appropriate for the CLL, including rituximab. A subsequent CIDP relapse after 15 months responded again to similar treatment, and the improvement has been maintained with 3-monthly rituximab infusions as sole ongoing therapy. The case suggests that CIDP refractory to conventional treatment may have associated pathology, in this case haematological malignancy, and that treating the malignancy can effectively treat the CIDP.

'The worm that got away': parainfectious atypical optic neuritis associated with schistosomiasis infection.

Although optic neuritis is commonly associated with multiple sclerosis, patients with atypical optic neuritis require further investigations to exclude other associated conditions. We report a woman presenting with cough, fatigue, atypical optic neuritis with chiasmitis. She responded partially to corticosteroids and we subsequently found she had a ground-glass lung nodule. Follow-up CT scan of thorax at 12 months showed new parenchymal lung lesions that suggested schistosomiasis. Further questioning by a respiratory physician identified, in retrospect, a previous exposure history; serological testing confirmed schistosoma infection. She was treated with praziquantel and slowly improved clinically, with radiological improvement in the optic chiasm, regression of the parenchymal lung lesions but with the ground glass nodule unchanged. We diagnosed parainfectious optic neuritis associated with schistosomiasis, based upon exposure history, serological confirmation and radiological features, together with the response to treatment, and having excluded other causes of an atypical optic neuritis.

Mononeuritis multiplex secondary to Lyme neuroborreliosis.

Lyme neuroborreliosis (LNB) typically presents as a painful radiculitis or a cranial mononeuropathy with lymphocytic meningitis (Bannwarth's syndrome). Isolated peripheral mononeuropathy or multiple mononeuropathy is less frequently recognised. A 58-year-old female with a background of IgA nephropathy and chronic kidney disease presented with a painful left ulnar neuropathy followed within 3 months by superficial radial neuropathy. Initial serum and cerebrospinal fluid (CSF) analysis were unremarkable; nerve conduction study was in keeping with a mononeuritis multiplex. A superficial radial nerve biopsy demonstrated inflammation with axonal injury consistent with a pathologically possible vasculitis. Borrelia antibodies were identified using enzyme-linked immunosorbent assay and immunoblot in serum consistent with active recent Lyme borreliosis. A 6-week course of doxycycline was initiated with gradual resolution of pain and improved power. A repeat nerve conduction study demonstrated improvement in sensory and motor responses. This case report identifies a peripheral nerve syndrome of a mononeuritis multiplex secondary to LNB in the absence of CSF pleocytosis with excellent outcome following antibiotic treatment. Peripheral nervous system manifestations of Lyme borreliosis can mimic a vasculitic neuropathy and therefore should be considered in individuals presenting with a painful mononeuritis multiplex.

Paroxysmal Hemicrania.

Paroxysmal hemicrania (PH) is a primary headache disorder belonging to the group of trigeminal autonomic cephalalgias(TACs). Patients typically experience intense lateralzsed headaches with pain primarily in the ophthalmic trigeminal distribution (V1) associated with superimposed ipsilateral cranial autonomic features. PH is distinguished from other TACs by an exquisite responsiveness to therapeutic doses of indomethacin. Patients may need to be maintained on indomethacin for several months before trials of reduction can be attempted. The disorder does have a tendency toward chronicity. PH is uncommon, but early recognition will prompt initiation of effective treatment to avoid unsuccessful trials of drugs effective in other primary headaches. As with other TACs, hypothalamic and trigeminovascular mechanisms are implicated in the pathophysiologic mechanism of PH. Neuroimaging findings in PH demonstrate a posterior hypothalamic activation similar to that observed in the other TACs. This review will address the epidemiology, clinical presentation, pathophysiology, evaluation, and treatment of PH.

Anterior spinal cord infarct: a rare yet disabling stroke.

We present a case which demonstrates the classical clinical symptoms and signs evident in an anterior spinal cord syndrome and explains the anatomical basis for the features seen with respect to the ascending and descending tracts in the spinal cord. It also demonstrates the clinical importance in conducting a detailed sensory examination to look for dissociated sensory loss and ascertaining the level of the pathology within the cord. The patient had made improvements following over a month of extensive rehabilitation on a specialist stroke unit.