Showing papers by "Norlinah Mohamed Ibrahim published in 2019"

Amelioration of Dystonic Opisthotonus in Pantothenate Kinase-Associated Neurodegeneration Syndrome with Absent "Eye-of-the-Tiger" Sign Following Bilateral Pallidal Deep Brain Stimulation.

Abstract: Pantothenate kinase-associated neurodegeneration (PKAN) is a rare autosomal recessive disorder causing progressive generalized dystonia characterized by neurodegeneration and brain iron accumulation (NBIA) due to pantothenate kinase 2 (PANK2) gene mutations. The radiological hallmark of PKAN, the “eyeof-the-tiger” sign, characterized by bilateral hypointensity with central hyperintensity in the globus pallidus on T2-weighted brain Magnetic Resonance Imaging (MRI) may be absent in some cases. Hence, clinicians may rely on phenotypic clues to aid diagnosis. Despite genetic advances, treatment for NBIA remains symptomatic. Bilateral globus pallidus internus deep brain stimulation (GPi-DBS) has been successful in PKAN patients refractory generalized dystonia. Herein we report a case of an atypical PKAN patient with severe dystonic opisthotonus and absent eye-of-the-tiger sign who obtained significant improvement following bilateral GPi-DBS. A 25-year-old Malay male was referred for progressive generalized dystonia that started at age 14. It began in the upper limbs with writing difficulties, and over the next five years, progressed to involve his face, neck, trunk, and lower limbs. By age 16, he had severe axial and craniocervical dystonia. He was treated with baclofen, clonazepam, diazepam, and trihexyphenidyl with minimal response. On examination, there was marked back arching (dystonic opisthotonus) with retrocollis that affected his posture and balance when standing and walking. There were prominent mouth-opening oromandibular dystonia and frequent action-induced painful facial and jaw dystonic spasms with speech difficulty. Both upper limbs were dystonic, with superimposed distal myoclonus (Video 1). Brain MRI showed absent eye-of-the-tiger sign (Fig. 1); however, the severe opisthotonic posturing raised a clinical suspicion of PKAN. Molecular analysis of the PANK2 gene 7 coding exons showed homozygous missense mutation NM_153638.2: c.332 T > A(rs71647828) in exon 1 with Leucine111Glutamine (L111Q) mutation, confirming the diagnosis of atypical PKAN. Failing oral therapies, he underwent bilateral GPi-DBS surgery. Day one, post-operatively, with the neurostimulator ON (amplitude 3.5 V; pulse-width 60 usec; frequency 130 Hz), there was a dramatic improvement in the dystonic opisthotonus, retrocollis, oromandibular, and upper limbs dystonia, and the patient was able to vocalize. The distal myoclonus had disappeared (Video 2, Segment 1). Dystonia severity assessment using BurkeFahn-Marsden Dystonia Rating Scale (BFMDRS) at one month demonstrated a 31.3% improvement on the motor scale score (preoperatively 80/120; postoperatively 55/120; Table 1). The disability scale score improved by only one point in walking (preoperatively 13/30; postoperatively 12/30), although the patient reported significant improvement in painful spasms, gait, and postural stability. After the surgery, the patient developed mild parkinsonism bilaterally, which improved with subsequent stimulation adjustments. The correction of axial dystonia and hand myoclonus remained sustained two years after the surgery (Video 2, Segment 2–4), with further improvement of the motor