Department of Neurology, University of Alabama at Birmingham, 1720 2nd Ave. South, SC271, Birmingham, AL, 35294-0017, USA.
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Curr Neurol Neurosci Rep. 2020 Oct 7;20(12):56. doi: 10.1007/s11910-020-01078-8.
To review the peripheral neurological complications of the acute hepatic porphyrias, as well as the latest advances in their pathophysiology and management.
The diagnosis of porphyric neuropathy remains challenging as varying neuropathic patterns are encountered depending on disease stage, including a non-length-dependent distribution pattern. The major pathophysiologic mechanism is δ-aminolevulinic acid (ALA)-induced neurotoxicity. The less restrictive blood-nerve barrier in the autonomic ganglia and myenteric plexus may explain the frequency of dysautonomic manifestations. Recently, a prophylactic small interfering RNA (siRNA)-based therapy that reduces hepatic ALA Synthase-1 mRNA was approved for patients with recurrent neuro-visceral attacks. Neurologists should appreciate the varying patterns of porphyric neuropathy. As with most toxin-induced axonopathies, long-term outcomes depend on early diagnosis and treatment. While the short-term clinical and biochemical benefits of siRNA-based therapy are known, its long-term effects on motor recovery, chronic pain, and dysautonomic manifestations are yet to be determined.
急性肝卟啉症的周围神经并发症，以及其病理生理学和治疗方面的最新进展。
由于不同的神经病变模式取决于疾病阶段，包括非长度依赖性分布模式，因此卟啉性神经病的诊断仍然具有挑战性。主要的病理生理机制是 δ-氨基乙酰丙酸（ALA）诱导的神经毒性。自主神经节和肌间神经丛中限制较少的血-神经屏障可能解释了自主表现频繁出现的原因。最近，一种基于小干扰 RNA（siRNA）的预防性治疗方法已被批准用于复发性神经内脏发作的患者，可降低肝 ALA 合酶-1 mRNA。神经科医生应该了解卟啉性神经病的不同模式。与大多数毒素诱导的轴突病变一样，长期预后取决于早期诊断和治疗。虽然已知 siRNA 为基础的治疗具有短期的临床和生化益处，但它对运动恢复、慢性疼痛和自主表现的长期影响仍有待确定。
