Dados do Trabalho

Título

Nusinersen and multidisciplinary approach in improvement of motor function in Spinal Muscular Atrophy type 3: a 2 years follow-up case report

RESUMO

Male patient initiated progressive weakness at 2-years-old. He was able to walk, but began to have frequent falls and difficulty climbing stairs. At the age of 14 he was referred to genetics due to a slow and progressive worsening. Denied dysphagia, dyspnea, speech or sphincter alterations. Upon examination, he presented with proximal and symmetric weakness, associated with lower limb atrophy and 4-membered areflexia. In 2018, at the age of 23, he was diagnosed with Spinal Muscular Atrophy (SMA) type 3 due to electroneurography and genetic examination. He began treatment with nusinersen in 2019, along with multidisciplinary follow-up. Motor function data were assessed by trained evaluators using Hammersmith Functional Rating Scale Expanded (HFMSE) and Ten-Meter Walking Test (10 MWT), according to the international recommendations on SMA standard of care, at the onset of treatment and reassessed every six months. After 2 years, the patient increased 5 points in the HFMSE and decreased 7s in the 10 MWT, which, according to the literature, defines clinically meaningful changes.
Discussion
SMA is an autosomal-recessive lower motor neuron disease causing progressive muscular atrophy and weakness. It is divided into four subtypes (0-4) according to age of symptoms onset and achieved motor landmarks. Nusinersen is an antisense oligonucleotide administered intrathecally, able to increase functional SMN protein levels, modifying SMA natural history. Although approved for any 5q SMA, most studies focus on nusinersen efficacy in infants and children, with data on adults limited to few observational studies and case series. This case shows clinical improvement in motor function of a SMA type 3 patient, even with the onset of treatment being twenty years after the onset of symptoms. This supports nusinersen efficacy in a long disease duration setting. Furthermore, multidisciplinary management is a well established therapy designed to address the psychosocial challenges of patients with SMA and cannot be excluded as an adjuvant in this patient’s enhancement.
Final comments
In adult SMA, outcome measures have not been as thoroughly standardized and validated. Although it is proven that a longer disease duration has a negative impact on treatment efficacy, this report indicates a satisfactory enhancement in unfavorable clinical conditions. Also, a multidisciplinary approach acts as an adjuvant for Nursinersen treatment in the improvement of motor function.

Palavras Chave

Spinal Muscular Atrophy