An interesting case of subacute sclerosing panencephalitis presenting with Balint’s syndrome and dysautonomia
Article information
Abstract
Subacute sclerosing panencephalitis (SSPE) is a rare, progressive neurodegenerative disorder caused by persistent aberrant measles virus infection. It is characterized by behavioral changes, cognitive decline with deterioration in academic performance, visual dysfunction, focal or generalized seizures ,myoclonus, spasticity, mutism and akinesia ultimately leading to a vegetative state. Balint’s syndrome, characterized by the triad of simultagnosia, optic ataxia, and oculomotor apraxia, as an initial presenting feature of SSPE is rare. Autonomic dysfunction in SSPE is attributed to central autonomic involvement, with decreased heart rate variability a predictor for arrhythmia and sudden cardiac death. We report an unusual case of a 22-year-old male presenting with features suggestive of Balint’s syndrome. Myoclonus and cognitive decline appeared 6 months after the first onset of symptoms, along with autonomic dysfunction. Thereafter, rapid progression of symptoms was noted. Cerebrospinal fluid and electroencephalography after the first symptom onset were consistent with a diagnosis of SSPE. The patient ultimately succumbed to his illness. Thus we highlight atypical presentation of SSPE with autonomic dysfunction. A high index of suspicion is needed for prompt and timely intervention.
Introduction
Subacute sclerosing panencephalitis (SSPE) is a progressive neurological disorder caused by a persistent and defective measles virus affecting children and adolescents. SSPE is a catastrophic neurological disorder characterized by progressive cognitive decline, neurobehavioral features, and myoclonus as the common initial presentations [1]. The triad of simultagnosia, optic ataxia, and oculomotor apraxia comprises Balint’s syndrome (BS), which occurs due to bilateral lesions of the posterior parietal and occipital lobes [2]. BS as a presenting feature of SSPE is extremely rare. In addition, autonomic dysfunction in SSPE has been much less studied and is attributed to central autonomic involvement, with decreased heart rate variability as a predictor for arrhythmia and sudden cardiac death [3]. Herein we report a case presenting features of BS and later developing generalized myoclonus and cognitive decline with bradycardia.
Case Report
A 22-year-old male presented with an 8-month history of inability to recognize faces, objects, pictures, and colors, although he was able to describe them in great detail. He had difficulty identifying the large size letters but could read the small ones. He could recognize and perceive some parts of an image but not the complete picture. He could recognize a key and a lock separately but could identify only one when they were presented simultaneously. He could not identify the faces of his relatives and often addressed his paternal cousin as his uncle. However, he was able to recognize them by hearing their voices. He lit incense sticks at their middle part instead of the tip. When asked to hold a teacup, tumbler, or marker, he would search the area looking for object before ultimately grasping it.
Three months after the symptom onset, his parents noted that he was unable to move his eyes when tracking an object and had to turn his head to view an object placed to either side. His parents thought that he had become blind and consulted an ophthalmologist. His visual acuity and color vision were normal. Six months after the symptom onset, he developed intermittent jerky movement of the bilateral upper limbs and trunk, along with cognitive impairment in the form of apathy, behavioral problems, and forgetfulness. He was then referred to our hospital for evaluation. Detailed questioning revealed a history of measles at the age of 5 years. His birth and developmental history were normal. His records had no mention of measles vaccination. His family history was negative. Blood pressure was 130/70 mmHg in the supine position and 100/54 mmHg at 3 minutes after standing, implying a postural drop. His pulse rate was 47 beats/minute and regular. Neurological examination revealed poor attention span hindering assessment of higher mental functions (Mini-Mental State Examination, 6/30 and forward and backward digit span, 2 and 0, respectively). Fundoscopy revealed bilateral normal oculi fundi. The patient was able to walk independently but tended to collide with walls on either side. Deep tendon reflexes were 2+, and the bilateral plantar response was flexor.
Routine blood tests and blood lactate levels were normal. Viral markers for human immunodeficiency virus, hepatitis B and C, and Venereal Disease Research Laboratory test were negative. Ultrasound of the abdomen and pelvis was normal. Electroencephalography revealed periodic sharp and slow wave complexes at varying intervals of 2 to 10 seconds (EEG machine setting–sweep: 15 mm/s; amplitude:10 μV/mm; low frequency filter: 1Hz, high frequency filter: 70Hz, notch filter: 50 Hz, longitudinal bipolar montage) (Figure 1). Brain magnetic resonance imaging (MRI) without contrast enhancement was suggestive of confluent areas of T2-weighted/fluid-attenuated inversion recovery hyperintensities in bilateral parieto-occipital lobes with mild volume loss (Figure 2). Cerebrospinal fluid (CSF) analysis revealed a total cell count of 3, protein level of 51.4 mg/dL, glucose level of 71 mg/dL, and immunoglobulin G (IgG) measles titer of 16,578 U/mL (serum IgG measles titer, 6,365 U/mL and CSF/serum quotient, 4.34). Tests for CSF oligoclonal band, neuromyelitis optica, myelin oligodendrocyte antibody, and BioFire (BioFire FilmArray Panels, BioFire Diagnostics) were negative. Serum and CSF autoimmune and paraneoplastic panels were negative. Nerve conduction studies were normal. Electrocardiography, two-dimensional echocardiography, and 48-hour Holter monitoring were normal except for sinus bradycardia.

Electroencephalography of the patient showing periodic sharp and slow wave complexes occurring at an interval of 2–3 seconds

Magnetic resonance imaging (MRI) of the brain demonstrating various sequences and findings
(A) Axial T2-weighted sequence showing hyperintense lesions (indicated by arrows) in the subcortical region. (B) Axial T1-weighted sequence with corresponding hypointense areas. (C, D) Axial fluid-attenuated inversion recovery sequences highlighting hyperintense regions consistent with edema or demyelination (arrows).
The patient received symptomatic treatment (clobazam 20 mg twice daily, levetiracetam 40 mg/kg/day, isoprenosine 100 mg/kg/day in three divided doses, and interferon alfa 3 million U/week). However, the patient continued to deteriorate and succumbed to the illness 1 month later.
Differential diagnoses included autoimmune encephalitis, viral encephalitis, neurosyphilis, progressive multifocal leukoencephalopathy, acute disseminated encephalomyelitis, atypical multiple sclerosis, paraneoplastic syndromes, leukodystrophies, mitochondrial encephalopathy, lactic acidosis and stroke-like episodes, and posterior reversible encephalopathy syndrome. However, the anti-measles antibody positivity, normal electroencephalogram, and MRI findings confirmed the diagnosis of SSPE.
Informed consent was obtained from the patient’s parents for publication of this report.
Discussion
The predominant manifestations in patients with SSPE are cognitive impairment, behavioral changes, myoclonus, irritability, attention deficits, dysexecutive function, psychiatric abnormalities, and poor scholastic performance [4]. Dystonia, parkinsonism, focal/generalized seizures, and schizophreniform symptoms are some atypical presentations of SSPE [5]. Affliction of the posterior parieto-occipital cortex causes BS, an unusual visuomotor dysfunction. In our patient, BS correlated with bilateral posterior parieto-occipital lesions, as evident on brain MRI (Figure 2). BS is a rare neurological disorder that presents with three key features of optic ataxia, oculomotor apraxia, and simultagnosia. Optic ataxia involves difficulty in reaching for objects under visual guidance, while oculomotor apraxia is characterized by difficulty in tracking the object. Similarly, our patient had difficulty grasping objects and moved his hands to search as if blind whenever he attempted to reach for an object. Also, he had to turn his head to perceive a clear view of an object placed on either side of him.
Simultagnosia, the third feature, refers to the inability to perceive more than one object at a time [2]. Our patient also struggled to identify large letters while easily reading smaller ones, demonstrating errors in reading. He also had prosopagnosia and visual agnosia, which correlated with the brain lesion on MRI.
The patient probably had features of BS for 5 to 6 months before the cognitive impairment and myoclonus became evident. This delay was attributed to a lack of knowledge and limited case reports on SSPE presenting with visuo-praxis deficits. Yapici [6] reported the first case of SSPE presenting as BS, which emphasized the need for immediate evaluation of a patient's cortical manifestations before obvious clinical progression. A study on heart rate variability and autonomic dysfunction in SSPE by Aydin et al. [7] concluded that SSPE patients had dysautonomia attributed to central autonomic network involvement. Their study suggested that dysautonomia in SSPE could be due to the involvement of central autonomic connections, epileptic activity, or high intracranial pressure. Reduced heart rate variability has been shown to be a predictor of arrhythmias and sudden death [7]. Interictal epileptogenic discharges that trigger autonomic neural discharges and cardiac arrhythmias are thought to be mediated by the cortex, hypothalamus, and limbic system [8]. However, there is only one reported case of SSPE presenting as BS [6]. Sinus bradycardia can be attributed to dysautonomia, hence autonomic functions should be explored in every case of SSPE.
We highlight BS as a rare initial presentation of SSPE. Such atypical presentations require a high index of suspicion. Since the disorder is prevalent in developing countries, clinicians must be aware of its presentation, even in the absence of myoclonus. Autonomic dysfunction portends a bad prognosis, as is exemplified by our case.
Notes
Conflicts of Interest
No potential conflict of interest relevant to this article was reported.
Author Contributions
Conceptualization: Parida S, Joshi D; Methodology, Software: Pandey N, Singh VK; Validation, Resources: Dhiman NR, Srivastava NK; Formal analysis, Data curation: Kumar A; Supervision: Joshi D; Writing–original draft: Parida S, Joshi D; Writing–review & editing: Parida S, Pandey N, Kumar A, Joshi D
Acknowledgments
We thank the patient and his parents for allowing us to present this study.