Freezing of gait in subacute sclerosing panencephalitis: When myoclonus is not the prime culprit for recurrent falls!

Dear Editor, Subacute sclerosing panencephalitis (SSPE) is a progressive, fatal, neurodegenerative disorder caused by persistent measles infection. It predominantly affects children and adolescents, with a greater prevalence in males. 1 While cognitive decline, behavioral changes, and myoclonus are usual initial symptoms, extrapyramidal symptoms, including chorea, dystonia, and parkinsonism, have been infrequently reported. 1 Gait in SSPE patients may be significantly affected by myoclonus and may be further worsened by associated extrapyramidal manifestations. 1 We report an adult SSPE patient with visual impairment and parkinsonism, along with significant freezing at gait initiation, resulting in repeated falls. A 27-year-old male, born of nonconsanguineous parentage with a normal birth and development history, developed acute-onset bilateral, painless diminution of vision 8 years ago, which progressed over a year, affecting his reading ability. Following a static course for the next 6 years, he developed insidious-onset, gradually progressive slowness in activities of daily living, along with cognitive decline and behavioral changes over the subsequent 6 months. Simultaneously, his gait worsened with recurrent falls, mostly forward, likely related to freezing at gait initiation. Subsequently, he developed right focal motor seizures. Neurological examination revealed an unremarkable fundus, hypophonic speech, along with bradykinesia and rigidity involving all four limbs. He had freezing at gait initiation, walked with short steps, and turned en bloc. The patient could not recover unaided on the pull test Video 1. Laboratory parameters, including complete blood picture, liver, renal, and thyroid function tests, returned normal. Electroencephalogram (EEG) revealed generalized, periodic, stereotyped, high-amplitude sharp and slow-wave discharges lasting 1–1. 5 s, occurring every 7–10 s Figure 1a. Brain magnetic resonance imaging (MRI) revealed bilateral frontal and parieto-occipital white-matter hyperintensities on T2 and fluid-attenuated inversion recovery sequences (FLAIR), along with temporo-occipital atrophy Figure 1b. In view of the characteristic electroencephalogram and brain MRI findings, SSPE was suspected, which was confirmed when cerebrospinal fluid examination revealed an elevated immunoglobulin G antimeasles antibody titer of 625 U/mL (normal <8 U/mL). There was no improvement with levodopa/carbidopa (100/25 mg), given up to three pills per oral four times a day for 3 months. His general condition and neurological status progressively worsened. "href": "Single Video Player", "role": "media-player-id", "content-type": "play-in-place", "position": "float", "orientation": "portrait", "label": "Video 1", "caption": "", "object-id": {"pub-id-type": "doi", "id": "", "pub-id-type": "other", "content-type": "media-stream-id", "id": "1ⱼ70z6ug0", "pub-id-type": "other", "content-type": "media-source", "id": "Kaltura"} Figure 1: Electroencephalogram and brain magnetic resonance imaging. (a). Electroencephalogram showing generalized, periodic, stereotyped, high-amplitude sharp and slow-wave discharges lasting 1–1. 5 s and occurring every 7–10 s. (b). Brain magnetic resonance imaging showing T2 and FLAIR white matter hyperintensities, along with atrophy involving parieto-occipital areas. Adult-onset SSPE patients are uncommon and may have a variable course, with a slow, indolent, or even static course for several years being reported, 2, 3 as was seen in our patient. Ocular and vision involvement has been reported in 10%–50% of SSPE patients, with retinal pathology being implicated in nearly two-thirds and cortical vision loss in 30% of patients. 4, 5 Considering the noncontributory fundus findings and parieto-occipital changes on brain MRI, cortical pathology appeared the likely cause of visual impairment in our patient. Excluding myoclonus, other abnormal movements have been reported in 1. 6%–56% of SSPE patients, with parkinsonism being reported in 6% of cases. 1 Movement disorders in SSPE result from basal ganglia and thalamus involvement, with enhanced basal ganglionic inhibitory output to the thalamus causing parkinsonism. 5 While ataxia, chorea, and dystonia may appear early in the disease course, parkinsonism is usually seen in the advanced stage. 1 Interestingly, our patient had visual impairment and parkinsonism with gait freezing sans myoclonus. Thus, SSPE should still be suspected when EEG and brain MRI findings are characteristic, even in the absence of myoclonus. In healthy individuals, gait is initiated by either cortex-mediated voluntary processing or limbic system-mediated emotional processing, followed by brainstem- and spinal cord-mediated automatic processes. 6 Inputs from the cerebral cortex and basal ganglia reach the mesencephalic locomotor region, which then projects to the pontomedullary reticular formation and subsequently to the spinal cord to regulate gait. 7 Movement initiation is associated with both cortical multisensory integration as well as motor cortex connections to the brainstem reticular formation and spinal cord. Temporo-parietal cortical involvement may affect multisensory integration involving proprioception, vision, and vestibular sensation, thereby causing incorrect production of motor programs, leading to gait freezing. 7 Brain MRI in our patient showed T2/ FLAIR white matter hyperintensities involving bilateral frontal and parieto-occipital regions, along with temporo-occipital atrophy, which likely affected both cortical multisensory integration as well as motor cortex connections to the brainstem, resulting in gait freezing. Declaration of patient’s consent The authors certify that they have obtained all appropriate patient consent forms. The patient understand that name and initials will not be published and due efforts will be made to conceal identity. Author contribution A. Research project: Conception: Niraj Kumar Organization: Nikita Dhar, Mritunjai Kumar, Ashutosh Tiwari, Niraj Kumar Execution: Nikita Dhar, Mritunjai Kumar, Ashutosh Tiwari B. Statistical analysis: Design: Execution: Review and Critique: C. Manuscript preparation: Writing of the first draft: Nikita Dhar Review and Critique: Mritunjai Kumar, Ashutosh Tiwari, Sweety Kumari, Niraj Kumar Ethical compliance statement The authors obtained approval from Institute ethics committee. We confirm that we have read the Journal’s position on issues involved in ethical publication and affirm that this work is consistent with those. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.