Dear Editor,

Oculogyric crisis (OGC) is an infrequent dystonic movement disorder marked by a prolonged, coordinated, and usually upward movement of the eyeball, enduring from seconds to several hours [1]. It is commonly associated with additional dyskinetic or dystonic movements, including neck dystonia, tongue protrusion, jaw clenching, and choreoathetosis [2]. OGC typically presents as an acute occurrence but may manifest a few weeks or months following a precipitating event [1]. Although OGC usually occurs as a side effect of medications such as antipsychotics, antiemetics, and antiseizure medications, it can also be observed secondary to various neurological conditions, including those affecting dopamine production, such as neurotransmitter disorders, or disorders affecting certain parts of the brain, such as multiple sclerosis, brainstem encephalitis, and Wilson’s disease [2]. Biotin-thiamine-responsive basal ganglia disease (BTBGD) is an autosomal recessive neurometabolic disorder. It is caused by pathogenic biallelic sequence variants in the SLC19A3 gene and is identified by episodes of subacute encephalopathy, presenting as seizures, confusion, extrapyramidal involvement, ataxia, and external ophthalmoplegia. Patients with BTBGD tend to have classical neuroimaging findings characterized by bilateral symmetric signal hyperintensity, swelling of the basal ganglia in the acute phase and atrophy and necrosis in the chronic phase. Classically, administering a high dose of thiamine improves symptoms within days [3].

Herein, we detail the case of a 6-year-old girl who was brought to the emergency room exhibiting symptoms including a two-day history of seizures, a widely opened mouth with tongue protrusion, and gait instability. A few months prior, she had sought medical attention at different institutions due to focal epilepsy, characterized by recurring episodes of intermittent sustained upward conjugate gaze without any alteration in consciousness. These episodes lasted less than one minute each and occurred three to four times per month. An electroencephalogram (EEG) was conducted, revealing no epileptiform abnormalities. Carbamazepine treatment was initiated, but there was no observed improvement. Notably, there was no history of recent infections or the intake of drugs or herbal medications. The child achieved developmental milestones at the appropriate ages and was born to consanguineous parents with no family history of inherited disorders.

Her physical exam revealed difficulty speaking and excessive drooling with an open mouth. A complete neurological assessment revealed a normal cranial nerve with dystonic movement of the lower extremities with hyperreflexia and clonus. The patient was admitted with a provisional diagnosis of acute disseminated encephalomyelitis to investigate the possibility of meningoencephalitis and mitochondrial disease. Initial laboratory tests, including a complete blood count, toxicity test, erythrocyte sedimentation rate, C-reactive protein, basic metabolic workup (ammonia, lactic acid, amino acid, and urine organic acid), and cerebrospinal fluid analysis, yielded no significant findings. The patient was started empirically on vancomycin (50 mg/kg/day), ceftriaxone (100 mg/kg/day), and acyclovir (20 mg/kg/day) for meningoencephalitis, but there was no improvement. In the initial stages of hospitalization, brain magnetic resonance imaging (MRI) was conducted. The MRI displayed pronounced hyperintense signals on fluid-attenuated inversion recovery and T2-weighted imaging. The signals were extensive and observed in the bilateral basal ganglia encompassing both putamen and caudate nuclei, as well as the medial thalami. Additionally, asymmetric multifocal areas of hyperintensity were identified in the bilateral cerebral cortex (Figure 1). These findings were highly indicative of a diagnosis of BTBGD; she improved significantly after starting on a high dose of thiamine (75 mg/kg/day) and biotin (10 mg/kg/day). After approximately one month, Sanger sequencing was performed, which revealed a homozygous pathogenic mutation in the SLC19A3 gene (NM_025243.4): c.1264A>G (p.Thr422Ala).

OGC is an acute dystonic reaction of the ocular muscles, which can be easily confused with tonic eye deviations, as observed in versive seizures; eye movement tics; paroxysmal tonic upward gaze; and retinal disease. Versive seizures exhibit forced and involuntary tonic or clonic head and eye deviations, resulting in prolonged abnormal head and eye positions resembling OGC. Notably, these seizures are accompanied by alterations in consciousness and abnormal EEG findings [4]. Eye movement tics, prevalent in children aged 6 to 12 years, involve rapid blinking and a stereotypical conjugate deviation of the eyes upward and outward. Similar to OGC, tics are typically briefer with less sustained ocular deviation [5]. Paroxysmal tonic upward gaze, with onset in infancy or early childhood, is characterized by episodes of sustained conjugate upward eye deviation. It can be differentiated from OGC by the presence of neck flexion and concurrent episodic ataxia. Research indicates that approximately 27% of patients eventually diagnosed with OGC were initially misdiagnosed with epilepsy [6]. In a similar vein, our patient was diagnosed with focal epilepsy and was prescribed carbamazepine without any improvement until the crisis began with obvious signs that needed attention.

While OGC typically manifests as a side effect of specific medications, it can also be associated with various neurological disorders affecting specific brain regions, as well as genetic and metabolic disorders impacting dopamine function [2]. In rare instances, reports have linked carbamazepine to OGC [7]. However, considering that OGC occurred before the initiation of carbamazepine in our case, it is unlikely to be the causative factor. Focal brain lesions at the basal ganglia level have also been identified as potential contributors to OGC [2]. These observations suggest the possibility that dysfunction in the nigrostriatal pathway may underlie the occurrence of OGC. Patients with BTBGD exhibit classical radiological features of bilateral basal ganglia changes, particularly in the caudate and putamen nuclei. They always present with movement disorders, including dystonia, cogwheel rigidity, and tremors. In addition, they may rarely present with chronic or slowly progressive dystonia [3]. Nevertheless, BTBGD patients have not been reported to experience an OGC as a precipitating illness. It can be challenging to recognize and accurately diagnose OGC. Therefore, clinicians should be aware of the other possible causes to avoid misdiagnosis.

This study reported a case of a patient with BTBGD who was initially misdiagnosed with focal epilepsy. Clinicians should be aware that OGC can be an early sign of BTBGD, necessitating investigation and prompt treatment to avoid misdiagnosis or complications resulting from delayed management.

Notes

Ethics Statement

Informed consent was obtained from the patient described in the case report.

Conflicts of Interest

The author has no financial conflicts of interest.

Funding Statement

None

Figure 1.

Axial magnetic resonance images of the brain during the acute phase. FLAIR (A), T2 sequence (B), and diffusion-weighted images (C) at the level of basal ganglia demonstrate symmetric signal hyperintensity of the caudate (yellow arrow), putamen (blue arrow), medial thalami (green arrow), and asymmetric multifocal areas of the bilateral cerebral cortex (black arrow). FLAIR, fluid-attenuated inversion recovery.

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References

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• Biotin Homeostasis and Human Disorders: Recent Findings and Perspectives
  Chrysoula-Evangelia Karachaliou, Evangelia Livaniou
  International Journal of Molecular Sciences.2024; 25(12): 6578.     CrossRef

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