Response to treatment in NMOSD: the Australasian experience.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is associated with significant morbidity and mortality. Several therapies have been recommended for NMOSD and more recently clinical trials have demonstrated efficacy for three monoclonal antibody therapies. We present a retrospective observational study of treatment response in NMOSD. METHODS: This was a retrospective, unblinded, observational study of treatment efficacy for rituximab and traditional immunosuppressive therapy in patients with AQP4 antibody positive NMOSD. Treatment efficacy was assessed using annualised relapse rates (ARR), time to first relapse and expanded disability status scale (EDSS) scores. RESULTS: Complete relapse and treatment data were available for 43/68 (63%) of AQP4 antibody positive NMOSD cases covering 74 episodes of treatment. In a time to first relapse analysis rituximab showed a risk ratio of 0.23 (95% CI 0.08 - 0.65) when compared with no treatment and there was a non-significant reduction in ARR of 35% compared to pre-treatment. ß-interferon (p = 0.0002) and cyclophosphamide (p = 0.0034) were associated with an increased ARR compared to pre-treatment. Rituximab (median 4.0 [range 0.0 - 7.0]; p = 0.042) and traditional immunosuppressive therapy (median 4.0 [range 0.0 - 8.0]; p = 0.016) were associated with a lower final EDSS compared to ß-interferon (median 6.0 [range 4.0 - 7.5]). CONCLUSIONS: These data provide additional support for the use of rituximab in preference to traditional immunosuppressive agents and MS disease modifying therapies as first line treatment of NMOSD.

MRI Patterns Distinguish AQP4 Antibody Positive Neuromyelitis Optica Spectrum Disorder From Multiple Sclerosis.

Neuromyelitis optica spectrum disorder (NMOSD) and multiple sclerosis (MS) are inflammatory diseases of the CNS. Overlap in the clinical and MRI features of NMOSD and MS means that distinguishing these conditions can be difficult. With the aim of evaluating the diagnostic utility of MRI features in distinguishing NMOSD from MS, we have conducted a cross-sectional analysis of imaging data and developed predictive models to distinguish the two conditions. NMOSD and MS MRI lesions were identified and defined through a literature search. Aquaporin-4 (AQP4) antibody positive NMOSD cases and age- and sex-matched MS cases were collected. MRI of orbits, brain and spine were reported by at least two blinded reviewers. MRI brain or spine was available for 166/168 (99%) of cases. Longitudinally extensive (OR = 203), "bright spotty" (OR = 93.8), whole (axial; OR = 57.8) or gadolinium (Gd) enhancing (OR = 28.6) spinal cord lesions, bilateral (OR = 31.3) or Gd-enhancing (OR = 15.4) optic nerve lesions, and nucleus tractus solitarius (OR = 19.2), periaqueductal (OR = 16.8) or hypothalamic (OR = 7.2) brain lesions were associated with NMOSD. Ovoid (OR = 0.029), Dawson's fingers (OR = 0.031), pyramidal corpus callosum (OR = 0.058), periventricular (OR = 0.136), temporal lobe (OR = 0.137) and T1 black holes (OR = 0.154) brain lesions were associated with MS. A score-based algorithm and a decision tree determined by machine learning accurately predicted more than 85% of both diagnoses using first available imaging alone. We have confirmed NMOSD and MS specific MRI features and combined these in predictive models that can accurately identify more than 85% of cases as either AQP4 seropositive NMOSD or MS.

Anticoagulant prescribing in patients with ischaemic stroke: what has changed over a decade?

A study at our institution conducted 10 years ago identified that warfarin was under-utilised in patients with atrial fibrillation. We replicated this study and compared the results. There was a significant increase in the proportion of patients appropriately anticoagulated (63% vs 9%, P < 0.001). Eighty-seven percent of eligible patients were appropriately anticoagulated on discharge (86% previously). Seventy-two percent of treated patients were prescribed a direct oral anticoagulant. Of these, 10% were discharged with a sub-therapeutic dose without obvious explanation.

Relapse Patterns in NMOSD: Evidence for Earlier Occurrence of Optic Neuritis and Possible Seasonal Variation.

Neuromyelitis optica spectrum disorders (NMOSD) and multiple sclerosis (MS) show overlap in their clinical features. We performed an analysis of relapses with the aim of determining differences between the two conditions. Cases of NMOSD and age- and sex-matched MS controls were collected from across Australia and New Zealand. Demographic and clinical information, including relapse histories, were recorded using a standard questionnaire. There were 75 cases of NMOSD and 101 MS controls. There were 328 relapses in the NMOSD cases and 375 in MS controls. Spinal cord and optic neuritis attacks were the most common relapses in both NMOSD and MS. Optic neuritis (p < 0.001) and area postrema relapses (P = 0.002) were more common in NMOSD and other brainstem attacks were more common in MS (p < 0.001). Prior to age 30 years, attacks of optic neuritis were more common in NMOSD than transverse myelitis. After 30 this pattern was reversed. Relapses in NMOSD were more likely to be treated with acute immunotherapies and were less likely to recover completely. Analysis by month of relapse in NMOSD showed a trend toward reduced risk of relapse in February to April compared to a peak in November to January (P = 0.065). Optic neuritis and transverse myelitis are the most common types of relapse in NMOSD and MS. Optic neuritis tends to occur more frequently in NMOSD prior to the age of 30, with transverse myelitis being more common thereafter. Relapses in NMOSD were more severe. A seasonal bias for relapses in spring-summer may exist in NMOSD.

The clinical profile of NMOSD in Australia and New Zealand.

Neuromyelitis optica spectrum disorders (NMOSD) are an inflammation of the central nervous system associated with autoantibodies to aquaporin-4. We have undertaken a clinic-based survey of NMOSD in the Australia and New Zealand populations with the aim of characterising the clinical features and establishing the value of recently revised diagnostic criteria. Cases of possible NMOSD and age and sex-matched controls with multiple sclerosis (MS) were referred from centres across Australia and New Zealand. Cases were classified as NMOSD if they met the 2015 IPND criteria and remained as suspected NMOSD if they did not. Clinical and paraclinical data were compared across the three groups. NMOSD was confirmed in 75 cases and 89 had suspected NMOSD. There were 101 controls with MS. Age at onset, relapse rates and EDSS scores were significantly higher in NMOSD than in MS. Lesions and symptoms referable to the optic nerve were more common in NMOSD whereas brainstem, cerebellar and cerebral lesions were more common in MS. Longitudinally extensive spinal cord lesions were seen in 48/71 (68%) of cases with NMOSD. Elevations of CSF, white cell count and protein were more common in NMOSD. We have confirmed a clinical pattern of NMOSD that has been seen in several geographical regions. We have demonstrated the clinical utility of the current diagnostic criteria. Distinct patterns of disease are evident in NMOSD and MS, but there remains a large number of patients with NMOSD-like features who do not meet the current diagnostic criteria for NMOSD and remain a diagnostic challenge.

Postural sway correlates with cognition and quality of life in Parkinson's disease.

BACKGROUND: The severity of Parkinson's disease (PD) is difficult to assess objectively owing to the lack of a robust biological marker of underlying disease status, with consequent implications for diagnosis, treatment and prognosis. The current standard tool is the Unified Parkinson's Disease Rating Scale (MDS-UPDRS), but this is hampered by variability between observers and within subjects. Postural sway has been shown to correlate with complex brain functioning in other conditions. This study aimed to investigate the relationship between postural sway, MDS-UPDRS and other non-motor measures of disease severity in patients with PD. METHOD: 25 patients with PD and 18 age-matched controls participated in the study. All participants underwent assessment of postural sway using a force plate, with eyes open and closed. In addition, participants underwent tests of cognition and quality of life: Montreal Cognitive Assessment (MoCA), Neuropsychiatry Unit Cognitive Assessment (NUCOG) and, for the patients, the Parkinson's Disease Questionnaire (PDQ-39-1), and assessment of clinical status using the motor component of the MDS-UPDRS. RESULTS: Patients swayed significantly more than controls. This was most obvious in the eyes-closed condition. Sway path length showed strong correlations with PDQ-39-1, MoCA and the verbal fluency component of the NUCOG, and, to a lesser degree, with the UPDRS-III in patients with PD. CONCLUSION: These results suggest that motor and non-motor symptoms of PD are associated in patients, and, in particular, that postural sway shows potential as a possible measure of underlying disease status in PD, either alone or in combination with other measures.

Botulinum neurotoxin for the treatment of movement disorders.

BACKGROUND: Botulinum neurotoxin (BoNT) is an exotoxin that causes neuromuscular weakness. BoNT serotypes A and B have been used for decades for the safe and effective treatment of various movement disorders, including some forms of focal dystonia. These conditions, such as cervical dystonia, hemifacial spasm, blepharospasm and spasmodic dysphonia, can have a substantial impact on patients' quality of life, but are often under-recognised. OBJECTIVE: The aim of this article is to describe the usefulness of BoNT for the treatment of movement disorders, including a description of its mechanism of action, mode of administration, indications and evidence of benefit. DISCUSSION: General practitioners have a vital role in the identification of patients with potentially treatable movement disorders such as cervical dystonia. Treatment with BoNT can improve patients' function, reduce pain and improve workforce participation. Patients require ongoing periodic injections by a trained neurologist to obtain long-term benefits with minimal side effects.

Tropheryma Whipplei Endocarditis: Case Report and Literature Review.

We describe a young man who initially presented with stroke and febrile illness. He was eventually diagnosed with Tropheryma whipplei endocarditis. This is a very rare condition and to the best of our knowledge, this is the first documented case of T. whipplei endocarditis in Australia and New Zealand regions. This report aims to increase awareness of clinicians of this very rare but potentially treatable condition. It is reasonable to exclude T. whipplei endocarditis when dealing with high-risk patients who are suspected for "culture-negative" endocarditis.

Incidence and prevalence of NMOSD in Australia and New Zealand.

OBJECTIVES: We have undertaken a clinic-based survey of neuromyelitis optica spectrum disorders (NMOSDs) in Australia and New Zealand to establish incidence and prevalence across the region and in populations of differing ancestry. BACKGROUND: NMOSD is a recently defined demyelinating disease of the central nervous system (CNS). The incidence and prevalence of NMOSD in Australia and New Zealand has not been established. METHODS: Centres managing patients with demyelinating disease of the CNS across Australia and New Zealand reported patients with clinical and laboratory features that were suspicious for NMOSD. Testing for aquaporin 4 antibodies was undertaken in all suspected cases. From this group, cases were identified who fulfilled the 2015 Wingerchuk diagnostic criteria for NMOSD. A capture-recapture methodology was used to estimate incidence and prevalence, based on additional laboratory identified cases. RESULTS: NMOSD was confirmed in 81/170 (48%) cases referred. Capture-recapture analysis gave an adjusted incidence estimate of 0.37 (95% CI 0.35 to 0.39) per million per year and a prevalence estimate for NMOSD of 0.70 (95% CI 0.61 to 0.78) per 100 000. NMOSD was three times more common in the Asian population (1.57 (95% CI 1.15 to 1.98) per 100 000) compared with the remainder of the population (0.57 (95% CI 0.50 to 0.65) per 100 000). The latitudinal gradient evident in multiple sclerosis was not seen in NMOSD. CONCLUSIONS: NMOSD incidence and prevalence in Australia and New Zealand are comparable with figures from other populations of largely European ancestry. We found NMOSD to be more common in the population with Asian ancestry.

Evaluation of a Regional Australian Nurse-Led Parkinson's Service Using the Context, Input, Process, and Product Evaluation Model.

OBJECTIVE: A nurse-led Parkinson's service was introduced at Canberra Hospital and Health Services in 2012 with the primary objective of improving the care and self-management of people with a diagnosis of Parkinson's disease (PD) and related movement disorders. Other objectives of the Service included improving the quality of life of patients with PD and reducing their caregiver burden, improving the knowledge and understanding of PD among healthcare professionals, and reducing unnecessary hospital admissions. This article evaluates the first 2 years of this Service. METHODS: The Context, Input, Process, and Product Evaluation Model was used to evaluate the Parkinson's and Movement Disorder Service. CONTEXT: The context evaluation was conducted through discussions with stakeholders, review of PD guidelines and care pathways, and assessment of service gaps. Input: The input evaluation was carried out by reviewing the resources and strategies used in the development of the Service. PROCESS: The process evaluation was undertaken by reviewing the areas of the implementation that went well and identifying issues and ongoing gaps in service provision. Product: Finally, product evaluation was undertaken by conducting stakeholder interviews and surveying patients in order to assess their knowledge and perception of value, and the patient experience of the Service. Admission data before and after implementation of the Parkinson's and Movement Disorder Service were also compared for any notable trends. CONTEXT: Several gaps in service provision for patients with PD in the Australian Capital Territory were identified, prompting the development of a PD Service to address some of them. Input: Funding for a Parkinson's disease nurse specialist was made available, and existing resources were used to develop clinics, education sessions, and outreach services. PROCESS: Clinics and education sessions were implemented successfully, with positive feedback from patients and healthcare professionals. However, outreach services were limited because of capacity constraints on the Parkinson's disease nurse specialist. Product: The Service has filled an important health need in the local context; 98.3% of patients surveyed reported that the Service met their needs and helped them understand their care plan, achieving the primary objective of improving patient self-management. Interviews with stakeholders provided positive feedback about the value and usefulness of the Service, and healthcare professionals reported improvement in their knowledge about PD management. The evaluation also identified ongoing gaps in service provision and highlighted areas for potential improvement. No discernible trends in admission rates before and after the implementation of the Service were identified. CONCLUSION: The introduction of a nurse-led PD service has had a positive impact on the provision of care for patients with PD and is a valued service. The evaluation highlighted some ongoing gaps in service provision and has generated some recommendations to address these.

P300 latency and neurocognitive functioning in recently diagnosed human immunodeficiency virus patients.

AIM: To assess the P300 latency and amplitude in recently diagnosed human immunodeficiency virus (HIV)-positive patients and compare the same with a healthy control group. Further an attempt was made to study the correlation between P300 amplitude and latency (in milliseconds) with neurocognitive functions. MATERIALS AND METHODS: Thirty newly diagnosed HIV-positive patients who on self report did not have any cognitive dysfunction were recruited. The patients were evaluated for P300 evoked response using the odd-ball paradigm, MMSE and a comprehensive neuropsychological battery. The P300 latencies were compared with 30 normal control subjects. RESULTS: The mean P300 latency (in milliseconds) of the HIV-positive subjects was significantly more than the healthy control group. The mean amplitude of HIV group was significantly less than the normal control group. On MMSE, 7 HIV-positive subjects had mild cognitive impairment (MMSE total score 20-23), six patients had minimal cognitive impairment (MMSE total score 24-27) and 17 patients had no cognitive impairment (MMSE total score >27). On neuropsychological test battery only three (10%) of HIV-positive subjects had cognitive dysfunction. There was negative correlation between P300 latency (in milliseconds) and MMSE total score and performance on Koh's Block subtest. CONCLUSION: P300 may be a reliable indicator of cognitive impairments in HIV patients.

Seizure type, antiepileptic drugs, and reproductive endocrine dysfunction in Indian women with epilepsy: a cross-sectional study.

BACKGROUND: There is paucity of data regarding occurrence of reproductive endocrine disorders in Asian women with epilepsy (WWE) on antiepileptic drug (AED) therapy. PURPOSE: To determine the occurrence of reproductive endocrine disorders in Indian WWE, by seizure type and the AED use. METHODS: Consecutive 427 reproductive age WWE receiving various AEDs were screened for the occurrence of menstrual abnormalities, weight change, and hirsutism. Of these, 53 WWE with menstrual disturbances and/or hirsutism were further evaluated for ovarian morphology and reproductive hormonal profile. RESULTS: Menstrual abnormalities and/or hirsutism were observed in 83 of 427 (19.4%) WWE irrespective of epileptic seizure type; of these, 50 (60.2%) received valproate, 21 (25.3%) received carbamazepine, 11 (13.3%) received phenytoin, and one (1.2%) received phenobarbitone as the primary AED. Almost half of valproate-treated women had significant weight gain and obesity. Among 53 of 83 women evaluated further, 23.5% and 63.6% of valproate-treated women, 25% and 58.3% of carbamazepine-treated women, and none and 20% of phenytoin-treated women had polycystic ovaries (PCO) and hyperandrogenemia (HA), respectively. Valproate-treated women had significantly higher frequency of polycystic ovarian syndrome (PCOS) (11.8% vs. 2.5%, p < 0.0001) and mean serum testrosterone levels (1.78 vs. 1.36 ng/ml, p = 0.03), compared with women treated with other AEDs. LIMITATIONS: Limitations include small number of women in antiepileptic subgroups and a high drop out rate in women who underwent ultrasound and endocrinological investigations. CONCLUSION: Menstrual abnormalities, weight gain, obesity, and PCOS are frequent and significantly higher in WWE receiving valproate, independent of seizure type.

Clinical profile of various sub-types of writer's cramp.

We profiled 141 consecutive patients of writer's cramp (WC). Simple WC (n=108) had a mean (SD) disease duration of 3.65 (2.7) years and a severity score of 2.8 (0.91) by Burke-Fahn-Marden (BFM) scale (handwriting score: 0-4 ), whereas complex WC (n=33) had a disease duration of 5.8 (2.81) years and severity score of 3.6 (0.52). Compared with focal WC, generalized WC cases had longer disease duration, severer disability, and were older. Mirror dystonia was seen in 65 patients (46.1%). Co-existent Meige's syndrome (n=4) and cervical dystonia (n=6) were seen. Some patients had abnormal posturing of the neck (n=5) and of the oromandibular region (n=3) only while writing. Those receiving botulinum toxin fared significantly better than those on oral therapy, at 1 month post treatment.

Efficacy of splinting and oral steroids in the treatment of carpal tunnel syndrome: a prospective randomized clinical and electrophysiological study.

OBJECTIVE: To study the efficacy of splinting and oral steroids in the management of carpal tunnel syndrome (CTS). DESIGN: Prospective, randomized, open-label, clinical and electrophysiological study with 3-month follow-up. MATERIALS AND METHODS: Forty patients with CTS were randomly divided into splint group (N-20), wearing splint in neutral position for 4 weeks; and steroid group (N-20), who received oral prednisolone 20 mg/day for 2 weeks followed by 10 mg/day for 2 weeks. Clinical and electrophysiological evaluations were done at baseline and at 1-month and 3-month follow-up. Independent 't' test and paired 't' test were used for statistical analysis. OUTCOME MEASURES: Primary outcome measure was the symptom severity score and functional status score. Secondary outcome measures were median nerve sensory and motor distal latency and conduction velocity. RESULTS: At the end of 3 months, statistically significant improvement was seen in symptom severity score and functional status score in both groups (P<0.001). Median nerve sensory distal latency and conduction velocity also improved significantly in both the groups at 3 months. Improvement in motor distal latency was significant (P=0.001) at 3 months in steroid group, while insignificant improvement (P=0.139) was observed in splint group. On comparing the clinical and electrophysiological improvement between the two groups, except for the functional status score, there was no significant difference at 3-month follow-up. Improvement in functional status score was significantly more in steroid group (P=0.03). CONCLUSION: There was significant improvement in both groups, clinically as well as electrophysiologically, at 3 months. On comparing the efficacy of the two treatment methods, except for the functional status score, there was no significant difference between the two groups.

Adrenoleukodystrophy manifesting as spinocerebellar degeneration.

X-linked adrenoleukodystrophy (XALD) is an inherited disorder of peroxisomal metabolism. Atypical presentations have been occasionally reported in literature. However, extrapyramidal and cerebellar manifestations are distinctly rare. We report a patient of X-linked adrenoleukodystrophy with cranial and cervical dystonia and neurological presentation resembling spinocerebellar degeneration followed by a brief review of relevant literature.

Transcranial magnetic stimulation: role in the evaluation of disability in multiple sclerosis.

BACKGROUND: In patients with multiple sclerosis (MS), transcranial magnetic stimulation (TMS) has shown significant prolongation of central motor conduction time (CMCT). Abnormal CMCT may reflect sub-clinical involvement of motor pathways and correlate with clinical motor disability. OBJECTIVE: To determine the diagnostic yield of TMS in MS and the possible correlation of TMS abnormalities with clinical disability. MATERIALS AND METHODS: Thirty patients with clinically definite MS presenting in acute relapse or with progressive disease course and 30 healthy controls were evaluated. TMS parameters evaluated included threshold intensity, motor evoked potentials (MEP) amplitudes and latencies and CMCT. Reassessment studies were done after three months. STATISTICAL ANALYSIS: Student t-test, Mann-Whitney U test and Spearman's rank correlation test were used to assess the relationships. RESULTS: Patients with MS had significantly higher threshold intensities, prolonged CMCT and reduced MEP amplitudes as compared to controls. Abnormalities in at least one parameter were observed in 86.7% of patients. When inter-side asymmetries in MEP latency and/or in CMCT were considered, the diagnostic yield increased to 96.7%. The diagnostic yield was 74.7% for visual evoked potentials, 13.3% for brainstem auditory evoked response and 10% for cerebrospinal fluid oligoclonal band. One MS patient without pyramidal or cerebellar dysfunction had prolonged CMCT. CMCT abnormalities correlated significantly with the degree of pyramidal signs, limb ataxia, intention tremor, dysdiadokokinesia and overall cerebellar score. In patients who had clinical improvement, follow-up studies showed improvement in CMCT parameters. CONCLUSION: TMS is a highly sensitive technique to evaluate cortico-spinal conduction abnormalities in MS that may have no clinical correlate and in monitoring the course of the disease. The effects of cerebellar dysfunction on TMS results need further evaluation.

Choice of therapy and mode of delivery in idiopathic intracranial hypertension during pregnancy.

Benign intracranial hypertension (BIH) or idiopathic intracranial hypertension (IIH) is a rare disorder of unknown etiology that is most often seen in obese women of reproductive age (19.3/100,000) and is reported only occasionally during pregnancy. Both pregnancy and exogenous estrogens are thought to promote IIH or worsen it. It can occur in any trimester during pregnancy, and the visual outcome is the same as for nonpregnant patients with IIH. There is no increase in fetal wastage; therapeutic abortion to limit its progression is not indicated, and subsequent pregnancies do not increase the risk of recurrence. Most therapies used during the nonpregnant state can also be used during pregnancy. The aim of treatment is to preserve vision and improve symptoms. Treatments include analgesics, diuretics, steroids, and serial lumbar punctures. When medical therapy fails, surgical procedures need to be considered. Although this condition has been reviewed often, the issue of mode of delivery, especially when papilledema has not resolved, is unclear. We report on 3 women with IIH during pregnancy and review the choice of therapy and mode of delivery.

Polyneuropathy in Osteosclerotic Myeloma Coexisting With Hyaline Vascular Castleman's Disease.

Peripheral neuropathy is usually the presenting feature of POEMS syndrome. Approximately 50% of patients with POEMS syndrome are associated with osteosclerotic myeloma, a rare variant of multiple myeloma, and some with Castleman's disease, an unusual lymphoproliferative disorder. The multicentric plasma cell variant of Castleman's disease is usually associated with systemic disorders rather than its localized form of mediastinal lymphoid hyperplasia characterized by hyalinization of follicles and interfollicular vascular proliferation. We report a 48-year-old woman who presented with progressive sensorimotor demyelinating polyradiculoneuropathy, bilateral optic disc edema, hepatosplenomegaly, generalized lymphadenopathy, and skin changes. There was associated thrombocytosis, hypothyroidism, hypoparathyroidism, mixed osteolytic and osteosclerotic bone lesions, monoclonal gammopathy of IgG lambda type, and hyaline vascular type of Castleman's disease. This combination of POEMS syndrome, osteosclerotic myeloma with a hyaline vascular type of Castleman's disease is uncommon.