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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]

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]

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]

Parkinson disease (PD) is a complex neurodegenerative disorder that can present heterogeneously with a combination of motor and non-motor symptoms. α-synuclein, a neuronal protein, can undergo aberrant conformational change resulting in the intra-neuronal accumulation of toxic oligomers that form Lewy bodies, the pathological hallmark of PD. There is evidence that pathological α-synuclein exhibits prion-like behaviour in its mode of transmission through the nervous system. The choice of initial dopaminergic treatments should be individually tailored but long term outcomes appear to be equivalent. There is level A evidence supporting the benefit of three different device-assisted therapies in treating troublesome motor fluctuations and dyskinesias. Stem cell transplantation as currently being trialled is predominantly a symptomatic therapy targeting only limited regions of the brain affected by PD, and will need to be proven to be not only as effective but as safe as currently available device-assisted therapies. New modes of treatment including active immunisation against oligomeric α-synuclein and drugs that alter cellular metabolism show some promise. The inability to effectively treat a range of non-motor, non-dopaminergic symptoms remains a major therapeutic challenge. [ABSTRACT FROM AUTHOR]

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]

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.

The article presents a case study of a 66-year-old man who presented to his general practitioner with a half-year history of tremor in his left hand. Tremor is a clinical problem in middle-aged and older patients. It was mentioned that several features of his condition are typical of parkinsonian tremor, which diminishes during limb movement. The man's wife stated that his posture had become more stooped over the past two years.

Recent advances in our understanding of the phenomenology, etiology, pathophysiology, and treatment of Tourette syndrome are discussed. Tourette syndrome appears to involve dysfunction of limbic and somatosensory “traffic” through the basal ganglia, within corticostriatal-thalamocortical circuits. Dynamic alterations in the balance of these inputs may dictate the manifestations (sensory, motor, affective, and behavioral) of the disorder at any given time. Individualized assessment and treatment are the keys to optimal treatment of this condition. [ABSTRACT FROM AUTHOR]

Parkinson disease (PD) is a multisystem neurodegenerative disorder that affects about 1% of the population over the age of 55 years and has mean age of onset of about 60 years. The Braak hypothesis proposes that the earliest pathological evidence of PD is found in the enteric nervous system, medulla and olfactory bulb, and only subsequently progresses (over years) to the substantia nigra and cortex. Non-motor symptoms, such as constipation, hyposmia and sleep disorders, may precede typical motor features of PD by several years. No treatment has been convincingly shown to slow PD progression (ie, a neuroprotective drug remains elusive). Symptomatic benefit from dopaminergic therapy is usually maintained throughout the course of the disease. The decision as to whether to commence treatment with either levodopa or a dopamine agonist needs to be individually tailored, but long-term outcomes appear to be equivalent. Advanced PD is complicated by the loss of non-dopaminergic neurones, resulting in symptoms that are largely unresponsive to dopaminergic therapy. Treatment with apomorphine, Duodopa or deep-brain stimulation surgery may be beneficial for selected patients with advanced PD. Non-motor symptoms, such as mood disorders, cognitive impairment, autonomic dysfunction and sleep disorders, are responsible for significant morbidity. Management often requires a multidisciplinary approach. [ABSTRACT FROM AUTHOR]

The article discusses concepts in the management of Parkinson disease (PD), a multisystem neurodegenerative disorder affecting nearly 1% of the population over the age of 55 years. Among the non-motor symptoms that may precede typical motor features of the disease by several years are constipation, hyposmia and sleep disorders. It notes that the loss of non-dopaminergic neurones complicate advanced PD. One of the non-motor symptoms that are responsible for significant morbidity is mood disorders.

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.

The article discusses a study which identified and quantified current deficiencies in primary and secondary stroke prevention and possible gains from optimal employment of thrombolysis. The study involved 259 consecutive patients admitted to a tertiary hospital stroke unit from January 24 2006 to January 10 2007 in Adelaide, South Australia. The researchers found that 183 patients had a disabling or fatal stroke, while 135 patients had at least one suboptimally managed risk factor.

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.

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]

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.

The article discusses the case of a female patient diagnosed with rhabdomyolysis and bilateral peroneal and tibial neuropathies caused by wearing and squatting in tight jeans. Topics discussed include the clinical presentation of the patient which include severe weakness of both ankles and impaired sensation, results of nerve conduction studies and the treatment of the patient intravenous hydration.

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.