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Context: Pelizaeus-Merzbacher Disease (PMD) is a rare X-linked recessive hypomyelinating leukodystrophy caused by mutations in the proteolipid protein 1 (PLP1) gene, associated with myelin sheath development and stability. The result is a broad spectrum of clinical phenotypes. Diagnosis is confirmed by genetic testing. Clinical features include hypotonia followed by progressive spasticity, nystagmus, ataxia and cognitive impairment. Males are more affected. Females are asymptomatic or present milder symptoms. Most cases arise from duplications, point and null mutations. Null mutations are associated with milder phenotypes. Brain Magnetic Resonance Imaging (MRI) may reveal hypomyelination. There is no disease modifying treatment for PMD. We aim to present the case of a woman with a novel variant of the PLP1 gene. Case report: A 38-year-old female presented with 23 years of progression of upper limb tremor, speech impairment, lower limb rigidity and urinary incontinence. She reported abnormal development of reading and writing skills. She had a brother with cognitive impairment, delayed motor development, gait disorder and generalized tonic-clonic seizures; and a sister with upper limb tremor, dysarthria and behavioral disorder. Hypomyelination was detected on brain MRI. Complete exome sequencing detected a novel likely pathogenic variant of PLP1 gene: ChrX(GRCh37):NC_000023.10:g.103041651del:NM _000533.3:c449del, p.Asp150AlafsTer10, heterozygous. Conclusions: The patient’s case resembles a milder form of PMD. This is supported by literature linking deletions and female sex to milder phenotypes. In 20 to 40% of cases with suggestive clinical findings, no PLP1 mutation is found. New studies are needed to identify other variants associated with PMD.

Introduction: Functional dependence is a common condition poststroke. The specialized care offered at the stroke unit can provide patients with better rehabilitation. We designed a study to evaluate risk factors for functional dependence at hospital discharge in a stroke unit. Design and setting: Prospective cohort study at Hospital Geral Roberto Santos. Methods: Patients were admitted within 72h of ictus. Functional dependence was defined as scores 3-5 on the modified Rankin Scale (mRS). Results: 389 patients were enrolled, with a mean age of 59.3 (±17.9) years, of whom 55.8% were men. The frequency of functional dependence at discharge was 57.1%, 50.3% at 30 days, and 38.8% at 90 days of the ictus. Higher risk of dependence at hospital discharge were associated with stroke recurrence [RR 1.2 (1.0 - 1.5)], polypharmacy [RR 1.3 (1.1 - 1.6)], female sex [RR 1.3 (1.1 - 1.6)], hemorrhagic stroke [RR 1.4 (1.2 - 1.7)], large artery atherosclerosis by TOAST [RR 1.6 (1.2 - 2.0)], hemorrhagic transformation [RR 1.57 (1.3 - 1.9)], infection [RR 1.7 (1.5 - 2.0)] and delirium [RR 1.8 (1.5 - 2.0)] during hospitalization. Conclusions: We have demonstrated a high frequency of functional dependence at hospital discharge from the stroke unit. Understanding which patients may have a worse functional outcome can be a good strategy to articulate access to the rehabilitation.

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