A milder form of molybdenum cofactor deficiency type A presenting as Leigh's syndrome-like phenotype highlighting the secondary mitochondrial dysfunction: a case report.

Background: Molybdenum cofactor deficiency (MoCD) (OMIM# 252150) is an autosomal-recessive disorder caused by mutations in four genes involved in the molybdenum cofactor (MOCO) biosynthesis pathway. Objectives: We report a milder phenotype in a patient with MOCS1 gene mutation who presented with a Leigh-like presentation. Case report: We present the case of a 10-year-old boy who was symptomatic at the age of 5 months with sudden onset of dyskinesia, nystagmus, and extrapyramidal signs following a febrile illness. Initial biochemical, radiological, and histopathological findings a Leigh syndrome-like phenotype; however, whole-exome sequencing detected compound heterozygous mutations in MOCS1 gene, c.1133 G>C and c.217C>T, confirming an underlying MoCD. This was biochemically supported by low uric acid level of 80 (110-282 mmol/L) and low cystine level of 0 (3-49), and a urine S-sulfocysteine at 116 (0-15) mmol/mol creatinine. The patient was administered methionine- and cystine-free formulas. The patient has remained stable, with residual intellectual, speech, and motor sequelae. Conclusion: This presentation expands the phenotypic variability of late-onset MoCD A and highlights the role of secondary mitochondrial dysfunction in its pathogenesis.

Clinical milestones as triggers for palliative care intervention in progressive Supranuclear palsy and multiple system atrophy.

not required for reviews.

Triggers for Referral to Specialized Palliative Care in Advanced Neurologic and Neurosurgical Conditions: A Systematic Review.

Background and Objectives: To systematically review the literature for the most suitable trigger criteria for referral to specialist palliative care services in life-limiting and life-threatening neurologic and neurosurgical conditions. Methods: Literature searches were conducted in Ovid MEDLINE and EMBASE (1990-December 2020). To be included, studies must have trigger/referral criteria clearly outlined, a ≥75% nononcology neurosciences population, and consensus or guidelines documents regarding palliative neurosciences or trigger/referral criteria. We excluded studies that had an oncologic or non-neurosciences population as the main focus of study, trigger and referral criteria not clearly outlined, and no primary or duplicative data. The protocol was registered with PROSPERO (CRD4202013579), and Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. The American Academy of Neurology Clinical Practice Guidelines Process Manual was used to assess for risk of bias. Results: Our search identified 1,748 publications, of which 22 articles met the eligibility criteria. Studies were considered in 2 main groups: (A) studies designed specifically to identify trigger criteria for referral to specialized neuropalliative care services (n = 9) and (B) studies that retrospectively reported the reason for referral to specialized palliative care or reflected a consensus statement among people with advanced neurologic illness (n = 13). Overall, the results suggest that several published referral triggers for specialized neuropalliative care are based on expert consensus. However, there is a growing body of literature providing evidence-based condition-specific triggers for multiple sclerosis, parkinsonism, amyotrophic lateral sclerosis, and dementia. Discussion: There is a growing body of research that outlines evidence-based referral triggers for neuropalliative care. The ambiguity of nomenclature surrounding referral triggers in the current literature and field of neuropalliative care was a limitation to this study. We suggest that condition-specific triggers are likely to be the most effective for identifying the appropriate patients and timing for referral to specialist palliative care. (PROSPERO registration number: CRD42020135791, crd.york.ac.uk/prospero).

Palliative Care Discussions in Multiple System Atrophy: A Retrospective Review.

OBJECTIVE: Multiple system atrophy (MSA) is an incurable neurodegenerative illness in which progressive symptoms, including stridor and acute laryngeal obstruction, occur. Advanced care planning and palliative care discussions in people living with MSA are not well defined. The aim of the present study is to evaluate advanced care planning and current practices in palliative care in MSA to identify opportunities for improving quality of care. METHODS: The study is a retrospective chart review assessing the focus and timing of palliative care discussions in people living with MSA. Some 22 charts were reviewed. RESULTS: A total of 22 patients were included. The most common symptoms were parkinsonism, orthostatic hypotension, GI/GU dysfunction, ataxia and gait impairment. Six patients had stridor. Of the palliative care discussions that took place, the most common topics were diagnosis, symptoms or symptom management, and prognosis. In the majority of patients who died and who had a do-not-attempt-resuscitation order, discussions surrounding resuscitation and goals of care took place only hours before death. CONCLUSIONS: There is no standard approach to advanced care planning and palliative care discussions in people living with MSA. We propose a framework to guide advanced care planning and palliative care discussions in MSA.