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This article presents an evidence‐based approach to the patient with newly diagnosed Parkinson disease (PD). It includes a discussion of the current understanding of the aetio‐pathogenesis of PD and of clinical features, both motor and non‐motor, that assist the clinician in making this diagnosis. An approach to the management of early stage PD is discussed, including emerging evidence of the benefits of physical exercise in this condition, and issues to consider in the selection of dopaminergic medication. The newly diagnosed patient with PD is often keen to know what the future holds for them, as they face this progressive neurodegenerative condition. While currently available medical therapies are symptomatic, rather than disease‐modifying, in nature, it is hoped that improved understanding of the aetio‐pathogenesis of PD will pave the way for future disease‐modifying therapies. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 66-year-old man with previously untreated, Rai stage III CLL presented with a four month history of progressive left sided sensory symptoms that affects both the upper and lower limbs of the patient. It mentions the presence of cervical myelopathy in spinal cord after examine with magnetic resonance imaging (MRI). It also mentions the CNS involvement by BTK-inhibition sensitive diseases like Waldenstrom Macroglobulinaemia.

Abstract: Objective: Ageing is accompanied by diminished practice-dependent plasticity. We investigated the effect of age on another plasticity inducing paradigm, repetitive transcranial magnetic stimulation (rTMS). Methods: Healthy young (n =15; 25±4years) and old (n =15; 67±5years) adults participated in two experiments. Motor evoked potentials (MEPs) were measured in the target muscle (first dorsal interosseus, FDI) and a remote muscle (abductor digiti minimi) during a set of single stimuli. Subjects then received real or sham inhibitory rTMS (intermittent subthreshold trains of 6Hz stimulation for 10min). MEPs were measured for 30min after rTMS. Results: In young adults, MEPs in the target FDI muscle were ∼15% smaller in the real rTMS experiment than in the sham rTMS experiment (P <0.026). In old adults, FDI MEP size did not differ between experiments. Conclusions: Advancing age is associated with reduced efficacy of inhibitory rTMS. Significance: This work has important implications for the potential therapeutic use of rTMS in stroke and neurological disease. [Copyright &y& Elsevier]

Abstract Chronic inflammatory demyelinating polyneuropathy (CIDP) may cause significant disability, but severe respiratory complications are uncommon. We describe the case of a 49-year-old man with clinical features of CIDP for 5 years who died of respiratory failure. Post-mortem findings of denervation in diaphragm muscle and axonal loss in phrenic nerve are presented. Severe ventilatory failure may occur in CIDP when neuropathy affects the respiratory muscles. Attention to early clinical features of respiratory insufficiency may facilitate the prevention of more severe features of respiratory failure. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented discussing several cases of convexity subarachnoid haemorrhage associated with bilateral internal carotid artery stenoses.

The article presents a case study of a 42-year-old man with segmental dystonia from long-term dextromethorphan abuse. The susceptibility of the patient to drug-induced dystonia is investigated. Explored is the association of the spectrum of movement disorders with N-methyl-D-aspartate (NMDA) receptor blockade.

Introduction: Foslevodopa/foscarbidopa, a soluble formulation of levodopa/carbidopa (LD/CD) prodrugs for the treatment of Parkinson's disease (PD), is administered as a 24-hour/day continuous subcutaneous infusion (CSCI) with a single infusion site. The efficacy and safety of foslevodopa/foscarbidopa versus oral immediate-release LD/CD was previously demonstrated in patients with PD in a 12-week, randomized, double-blind, phase 3 trial (NCT04380142). We report the results of a separate 52-week, open-label, phase 3 registrational trial (NCT03781167) that evaluated the safety/tolerability and efficacy of 24-hour/day foslevodopa/foscarbidopa CSCI in patients with advanced PD. Methods: Male and female patients with levodopa-responsive PD and ≥ 2.5 hours of "Off" time/day received 24-hour/day foslevodopa/foscarbidopa CSCI at individually optimized therapeutic doses (approximately 700–4250 mg of LD per 24 hours) for 52 weeks. The primary endpoint was safety/tolerability. Secondary endpoints included changes from baseline in normalized "Off" and "On" time, percentage of patients reporting morning akinesia, Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Parkinson's Disease Sleep Scale–2 (PDSS-2), 39-item Parkinson's Disease Questionnaire (PDQ-39), and EuroQol 5-dimension questionnaire (EQ-5D-5L). Results: Of 244 enrolled patients, 107 discontinued, and 137 completed treatment. Infusion site events were the most common adverse events (AEs). AEs were mostly nonserious (25.8% of patients reported serious AEs) and mild/moderate in severity. At week 52, "On" time without troublesome dyskinesia and "Off" time were improved from baseline (mean [standard deviation (SD)] change in normalized "On" time without troublesome dyskinesia, 3.8 [3.3] hours; normalized "Off" time, −3.5 [3.1] hours). The percentage of patients experiencing morning akinesia dropped from 77.7% at baseline to 27.8% at week 52. Sleep quality (PDSS-2) and quality of life (PDQ-39 and EQ-5D-5L) also improved. Conclusion: Foslevodopa/foscarbidopa has the potential to provide a safe and efficacious, individualized, 24-hour/day, nonsurgical alternative for patients with PD. Trial Registration Number: ClinicalTrials.gov identifier NCT03781167. [ABSTRACT FROM AUTHOR]

Background Patients with Parkinson disease ( PD) commonly experience motor fluctuations and dyskinesias in response to oral dopaminergic medications. Affected patients may benefit from device-assisted therapy, such as medication infusion or deep brain stimulation surgery. This is the first Australian study of the long-term adherence to apomorphine infusion ( AI) in patients with PD. Aims To assess the adherence to AI in patients with PD in a single centre over a 10-year period and to find the reasons for discontinuation in patients who discontinued AI. Methods This is an observational study of patients with PD treated with AI between 2004 and 2014. Outcome measures included changes in motor function and quality of life following AI, change in dose of other dopaminergic medications following AI, duration of infusion, adverse effects, reasons for cessation of AI and subsequent treatment after cessation. Results Mean duration of AI was 21.65 months. No patient achieved apomorphine monotherapy, and the mean reduction in the levodopa-equivalent dose of other dopaminergic medications after AI was 22.7%. The benefit of AI on motor function and quality of life was rated as 'much improved' or 'better' in 83% of patients. The most common reasons for discontinuation of AI were adverse effects and inadequate motor benefit. Most patients who discontinued AI were subsequently treated with another device-assisted therapy. Conclusion AI is an effective therapy for severe motor response complications in PD, especially in the short and medium term. However, many patients cannot be maintained on AI in the longer term. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented regarding a 64 year old businesswoman presented with treatment-resistant depression and multiple system atrophy (MSA) wherein electroconvulsive therapy (ECT) 3 times per week improved her physical symptoms.

Background: Levodopa is the most effective symptomatic therapy for Parkinson's disease, but patients with advanced Parkinson's disease develop motor fluctuations with chronic oral levodopa therapy. Foslevodopa-foscarbidopa is a soluble formulation of levodopa and carbidopa prodrugs that is delivered as a 24-h/day continuous subcutaneous infusion, and we aimed to assess the safety and efficacy of this formulation in patients with advanced Parkinson's disease.Methods: A 12-week randomised, double-blind, double-dummy, active-controlled study was done at 65 academic and community study centres in the USA and Australia. Patients with levodopa-responsive advanced Parkinson's disease inadequately controlled on current therapy, including at least 2·5 h of average daily off time, were randomly assigned (1:1) to continuous subcutaneous infusion of foslevodopa-foscarbidopa plus oral placebo or to oral immediate-release levodopa-carbidopa plus continuous subcutaneous infusion of placebo solution. Randomisation was stratified by site by means of a permutated-block schedule with a block size of two. The participants, treating investigators, study site personnel, and sponsor were masked to treatment group allocation. The primary and first key secondary endpoint in the hierarchical testing strategy were change from baseline to week 12 in on time without troublesome dyskinesia and off time, respectively; both endpoints were evaluated by an intention-to-treat analysis applying a mixed model for repeated measures analysis. Safety and tolerability were assessed throughout the study. The study is completed and is listed on ClinicalTrials.gov, NCT04380142.Findings: Between Oct 19, 2020, and Sept 29, 2021, of 270 participants screened and 174 enrolled, 141 were randomly assigned and received continuous subcutaneous infusion of foslevodopa-foscarbidopa plus oral placebo capsules (n=74) or oral encapsulated immediate-release levodopa-carbidopa plus continuous subcutaneous infusion of placebo solution (n=67). Compared with levodopa-carbidopa, foslevodopa-foscarbidopa showed a significantly greater increase in on time without troublesome dyskinesia (model-based mean [SE] 2·72 [0·52] vs 0·97 [0·50] h; difference 1·75 h, 95% CI 0·46 to 3·05; p=0·0083) and a significantly greater reduction in off time (-2·75 [0·50] vs -0·96 [0·49] h; difference -1·79 h, -3·03 to -0·54; p=0·0054). Hierarchical testing ended after the first secondary endpoint. Adverse events were reported in 63 (85%) of 74 patients in the foslevodopa-foscarbidopa group versus 42 (63%) of 67 in the levodopa-carbidopa group, and incidences of serious adverse events were similar between the groups (six [8%] of 74 vs four [6%] of 67, respectively). The most frequent adverse events in the foslevodopa-foscarbidopa group were infusion site adverse events (erythema 20 [27%]), pain 19 [26%]), cellulitis (14 [19%]), and oedema (nine [12%]), most of which were non-serious and mild-moderate in severity. The only system organ class that had more than one serious adverse event in the foslevodopa-foscarbidopa group was infections and infestations (catheter site cellulitis [one [1%]] and infusion site cellulitis [one [1%]). Adverse events led to premature discontinuation of study drug in 16 (22%) of 74 participants in the foslevodopa-foscarbidopa group versus one (1%) of 67 participants in the oral levodopa-carbidopa group.Interpretation: Foslevodopa-foscarbidopa improved motor fluctuations, with benefits in both on time without troublesome dyskinesia and off time. Foslevodopa-foscarbidopa has a favourable benefit-risk profile and represents a potential non-surgical alternative for patients with advanced Parkinson's disease.Funding: AbbVie. [ABSTRACT FROM AUTHOR]

The article examines the case of a patient with dystonia-parkinsonism due to pallidal and nigral necrosis following heroin overdose. The patient has a history of marijuana use, post-traumatic stress disorder, depression and amphetamine-induced psychosis. Examination of the patient revealed right hemichorea and impairment of left-sided fractioned finger movements. It revealed that the evolution from hemichorea to dystonia was owing to acute and subacute effect of pallidal anoxia, respectively.

Summary: We report a case of low cerebrospinal fluid (CSF) pressure headache from a CSF leak diagnosed by magnetic resonance imaging (MRI) treated successfully with a cervical epidural blood patch. The epidural needle was guided by intensive imaging followed by insertion of an epidural catheter in the C3/C4 interspace and placement confirmed with contrast. This report is the first to highlight a technique which may be useful especially in identifying the optimum amount of blood required in the cervical epidural space as well as allowing for repeat blood patches to be performed without an increase in risk associated with the repeat procedure. [Copyright &y& Elsevier]

The original article can be found online at https://doi.org/10.1007/s40120-023-00533-1. B Correction: Neurol Ther b https://doi.org/10.1007/s40120-023-00533-1 In the sentences beginning "At baseline,..". and "The reduction of early morning..". in the section "Efficacy" under the heading "Results" in this article, the I n/N i values '129/238, 20/139, 25/125 and 56/125' were incorrect and the correct sentences should have read as follows: At baseline, 77.7% ( I n/N i = 129/166) of patients experienced morning akinesia, which decreased to 19.2% ( I n/N i = 20/104) at week 26, and 27.8% ( I n/N i = 25/90) at week 52. In the sentence beginning 'The reduction of "Off" time is particularly exemplified by..'. under the heading "Discussion", the value '(changed from 17.5% at baseline to 63.0% at week 52)' should have read '(changed from 17.5% at baseline to 62.2% at week 52)'. [Extracted from the article]

In Australia 1% of individuals aged over 50 years have Parkinson disease ( PD). Guidance for commencing device-assisted therapies ( DAT) for PD in Australia was developed based on a review of European recommendations and their relevance to the local clinical setting. An online survey and teleconference discussions were held by a group of eight local movement disorder experts to develop consensus. Referral to a movement disorder specialist and consideration of DAT is appropriate when motor fluctuations cause disability or reduced quality of life, response to treatment is inconsistent or motor fluctuations and dyskinesias require frequent treatment adjustment without apparent benefit and levodopa is required four or more times daily. Three types of DAT are available in Australia for patients with PD: continuous subcutaneous apomorphine; continuous levodopa-carbidopa intestinal gel infusion; and deep brain stimulation. All improve consistency of motor response. The most important aspects when considering which DAT to use are the preferences of the patient and their carers, patient comorbidities, age, cognitive function and neuropsychiatric status. Patients and their families need to be provided with treatment options that are suitable to them, with adequate explanations regarding the recommendations and comparison of potential device-related complications. DAT are best managed, where possible, in a specialist centre with experience in all three types of therapy. Proactive and early management of symptoms during disease progression is essential to maintain optimally motor responses and quality of life in patients with PD. [ABSTRACT FROM AUTHOR]

A 35 year old woman presented with bilateral foot drop and numbness following repetitive squatting while wearing “skinny” jeans. Her examination demonstrated bilateral, severe, global weakness of ankle and toe movements, somewhat more marked on the right, absent ankle jerks and impaired sensation over the lateral aspects of both lower legs and the dorsum and soles of both feet. Her lower limbs were markedly oedematous and the jeans had to be cut off for removal. Investigations showed a creatine kinase level of 73215 IU/L with normal renal function. CT scan of the lower limbs demonstrated myonecrosis in the posterior calf muscles. Nerve conduction studies showed bilateral conduction block between the popliteal fossa and fibular head of the common peroneal nerves. Compound muscle action potential amplitudes of the tibial nerves were also diminished with stimulation in the popliteal fossa, compared with the ankle. The sural and superficial peroneal sensory responses were normal but the right medial plantar SAP was absent and the left medial plantar SAP was markedly reduced in amplitude. With conservative therapy, the patient’s oedema and neurological function improved and she was discharged after regaining independence with her mobility four days later. We postulate that the patient’s peroneal neuropathies were the result of compression between the biceps femoris tendon and fibular head as a result of squatting while the tibial neuropathies were likely caused by compression of the nerves in the posterior compartment of the calf by oedematous muscles which had undergone ischaemic myonecrosis as a result of squatting. The wearing of “skinny” jeans had likely potentiated the tibial neuropathies by causing a compartment syndrome as the lower legs swelled. [ABSTRACT FROM AUTHOR]

Summary: Background: Whether intravenous tissue plasminogen activator (alteplase) is effective beyond 3 h after onset of acute ischaemic stroke is unclear. We aimed to test whether alteplase given 3–6 h after stroke onset promotes reperfusion and attenuates infarct growth in patients who have a mismatch in perfusion-weighted MRI (PWI) and diffusion-weighted MRI (DWI). Methods: We prospectively and randomly assigned 101 patients to receive alteplase or placebo 3–6 h after onset of ischaemic stroke. PWI and DWI were done before and 3–5 days after therapy, with T2-weighted MRI at around day 90. The primary endpoint was infarct growth between baseline DWI and the day 90 T2 lesion in mismatch patients. Major secondary endpoints were reperfusion, good neurological outcome, and good functional outcome. Patients, caregivers, and investigators were unaware of treatment allocations. Primary analysis was per protocol. This study is registered with ClinicalTrials.gov, number NCT00238537. Findings: We randomly assigned 52 patients to alteplase and 49 patients to placebo. Mean age was 71·6 years, and median score on the National Institutes of Health stroke scale was 13. 85 of 99 (86%) patients had mismatch of PWI and DWI. The geometric mean infarct growth (exponential of the mean log of relative growth) was 1·24 with alteplase and 1·78 with placebo (ratio 0·69, 95% CI 0·38–1·28; Student''s t test p=0·239); the median relative infarct growth was 1·18 with alteplase and 1·79 with placebo (ratio 0·66, 0·36–0·92; Wilcoxon''s test p=0·054). Reperfusion was more common with alteplase than with placebo and was associated with less infarct growth (p=0·001), better neurological outcome (p<0·0001), and better functional outcome (p=0·010) than was no reperfusion. Interpretation: Alteplase was non-significantly associated with lower infarct growth and significantly associated with increased reperfusion in patients who had mismatch. Because reperfusion was associated with improved clinical outcomes, phase III trials beyond 3 h after treatment are warranted. Funding: National Health and Medical Research Council, Australia; National Stroke Foundation, Australia; Heart Foundation of Australia. [Copyright &y& Elsevier]

The article presents a case study of a 63 years old woman with cerebellar syndrome with seizures, hypomagnesaemia, and pantoprazole. It discusses the symptoms including dizziness, lethargy, and anorexia. It also presents information on the use of proton pump inhibitors, electrocardiogram results, and computed tomography scan results of the chest.

Background: Whether intravenous tissue plasminogen activator (alteplase) is effective beyond 3 h after onset of acute ischaemic stroke is unclear. We aimed to test whether alteplase given 3-6 h after stroke onset promotes reperfusion and attenuates infarct growth in patients who have a mismatch in perfusion-weighted MRI (PWI) and diffusion-weighted MRI (DWI).Methods: We prospectively and randomly assigned 101 patients to receive alteplase or placebo 3-6 h after onset of ischaemic stroke. PWI and DWI were done before and 3-5 days after therapy, with T2-weighted MRI at around day 90. The primary endpoint was infarct growth between baseline DWI and the day 90 T2 lesion in mismatch patients. Major secondary endpoints were reperfusion, good neurological outcome, and good functional outcome. Patients, caregivers, and investigators were unaware of treatment allocations. Primary analysis was per protocol. This study is registered with ClinicalTrials.gov, number NCT00238537.Findings: We randomly assigned 52 patients to alteplase and 49 patients to placebo. Mean age was 71.6 years, and median score on the National Institutes of Health stroke scale was 13. 85 of 99 (86%) patients had mismatch of PWI and DWI. The geometric mean infarct growth (exponential of the mean log of relative growth) was 1.24 with alteplase and 1.78 with placebo (ratio 0.69, 95% CI 0.38-1.28; Student's t test p=0.239); the median relative infarct growth was 1.18 with alteplase and 1.79 with placebo (ratio 0.66, 0.36-0.92; Wilcoxon's test p=0.054). Reperfusion was more common with alteplase than with placebo and was associated with less infarct growth (p=0.001), better neurological outcome (p<0.0001), and better functional outcome (p=0.010) than was no reperfusion.Interpretation: Alteplase was non-significantly associated with lower infarct growth and significantly associated with increased reperfusion in patients who had mismatch. Because reperfusion was associated with improved clinical outcomes, phase III trials beyond 3 h after treatment are warranted. [ABSTRACT FROM AUTHOR]