HYPOGLYCEMIC HEMIPLEGIA IS occasionally seen in conjunction with central nervous system dysfunction. Although neurological symptoms due to hypoglycemia are transient when glucose treatment is provided immediately, severe prolonged hypoglycemia is usually fatal. In this report, we describe a case of transient hemiplegia followed by permanent encephalopathy, caused by prolonged hypoglycemia following a substantial insulin injection, that involved various abnormalities on multiple neurophysiological and neuroimaging modalities.
A 21-year-old left-handed male patient was admitted with a 19-h history of coma after substantial insulin injection for suicide attempt. Although the patient recovered from coma 3 days after injury, he experienced transient hemiplegia followed by permanent brain damage. Electroencephalogram (EEG), brain magnetic resonance imaging (MRI), and brain single-photon emission computed tomography (SPECT) identified the localization of this dysfunction, but consistency between clinical symptoms and brain images changed depending on the course of treatment. Transient hemiplegia corresponded to abnormal waveforms on EEG and decreased cerebral blood flow on SPECT, whereas persistent dysfunctions corresponded to abnormal brain regions on MRI and SPECT.
A 21-year-old left-handed male patient was admitted to hospital with a 19-hour history of coma following a suicide attempt by an overdose of nitrazepam (30 mg orally) and a substantial injection of intermediate-acting insulin (s.c.). His father had diabetes mellitus and anxiety disorder, and he had neither history of diabetes mellitus, mental illness, nor alcohol consumption. His score on the Glasgow coma scale upon admission was E 1 V 1 M 1, and vital signs were as follows: blood pressure, 151/66 mmHg; heart rate, 87 b.p.m., respiratory rate, 24 b.p.m.; and body temperature, 36.6°C. His blood glucose level was 24 mg/dL upon admission but recovered immediately after continuous i.v. glucose injection. Arterial blood gas measurement under 10 L/min oxygen mask was pH 7.343, pO2 308 Torr (4.11 kPa), pCO2 49.8 Torr (0.664 kPa), and base excess 0.64. He developed respiratory failure after glucose injection and required intensive respiratory care. Three days after admission, the patient was able to vocalize and open his eyes, but move only his left arm and leg. In addition, he could not follow any instructions or eat anything by himself.
The course of acquired brain imaging is shown in Fig. 1. Two weeks after injury, brain magnetic resonance imaging (MRI) showed T2-weighted high signal and fluid-attenuated inversion recovery (FLAIR) mixed signal areas in the bilateral orbitofrontal cortex and reduced volume in the left hippocampal region (Fig. 1d), and electroencephalogram (EEG) at rest showed delta waves in the left fronto-polar region and indicated an absence of alpha waves in the bilateral occipital region (Fig. 1a). One month after injury, technetium-99m ethyl cysteinate dimer single-photon emission computed tomography (SPECT) showed significantly reduced cerebral blood flow over the lateral side of the left cerebral cortex and in the bilateral hippocampal region (Fig. 1f).
Right hemiplegia lasted for 1 month but gradually recovered in the course of rehabilitation. Six months after injury, the patient was able to move his arms and legs symmetrically and follow easy instructions, but still experienced apathy, anarithmia, transcortical aphasia, lack of facial expression, and severe impairment of short-term memory and higher intellectual processes. Follow-up EEG improved in the occipital region except for the left fronto-polar region (Fig. 1b), while MRI and SPECT data showed little improvement in the abnormal regions (Fig. 1e,g, respectively). Twelve months after injury, EEG improved to within the normal range (Fig. 1c), but the clinical symptoms showed little improvement between 6 and 12 months after the injury.
We acquired written informed consent from the patient and his family members for publication of this case report 12 months after the injury.
Hypoglycemia is seen as one of the major adverse effects of insulin therapy for patients with diabetes mellitus. The major symptoms of hypoglycemia include not only pallor, diaphoresis, and tachycardia related to increased activity in the sympathetic nerve, but also headache, dizziness, confusion, seizure, and loss of consciousness related to central nervous system dysfunction. In conjunction with neurological disturbance, hemiplegia is occasionally seen with hypoglycemia. If glucose complement is performed immediately, hemiplegia is a transient condition, and patients typically recover without any subsequent complications. Although the theoretical mechanism of hemispheric encephalopathy induced by hypoglycemia is still unknown, several explanations have been proposed, including cerebral vasospasm, narrow arteries, and focal vulnerability.[1-5]
This case is very rare in terms of survival from long-term severe hypoglycemia, and a19-h delay in glucose therapy. Based on historical research of insulin-induced hypoglycemic therapy in psychiatry, irreversible brain damage occurs when a hypoglycemic coma lasts >30 min. Any further long delay results in fatal condition. One possible explanation as to how this patient survived the prolonged hypoglycemic coma may be that prior to the insulin injection, he took a benzodiazepine overdose. This may have decreased his brain metabolism, thereby preventing the brain tissue damage associated with glucose deficiency.[3, 6]
The patient had right hemiplegia during the early course of treatment, and EEG and SPECT data showed abnormalities significantly in the left hemisphere consistent with clinical symptoms. Although the improvement observed on follow-up EEG was consistent with recovery from hemiplegia, cerebral blood flow shown on SPECT was not improved in the left hemisphere. The region of little improvement in the left temporo-parietal cortex has the essential function of connection and integration between Broca's and Wernicke's areas. Damage in this region can cause transcortical aphasia. One possible reason for improvement of hemiplegia may be due to the patient's hemispheric specialization. His dominant hemisphere was left because of aphasia, but it is also possible that the patient's dominant hemisphere might be incompletely determined. Therefore, compensatory relocalization of cortical functions may more easily occur compared to a right-handed person.
Follow-up MRI and SPECT showed little improvement in the bilateral orbitofrontal cortex, consistent with frontal lobe dysfunctions such as apathy, lack of facial expression, and higher intellectual processes (e.g. Phineas Gage's case). Reduced cerebral blood flow was also shown in the hippocampus, consistent with short-memory disturbance. These residual dysfunctions corresponded to the abnormalities of brain regions in both initial and follow-up MRI and SPECT.
In conclusion, we report a case of transient hemiplegia followed by permanent encephalopathy caused by prolonged hypoglycemia using multiple neurophysiological and neuroimaging instruments. EEG, MRI, and SPECT identified the localization of this dysfunction, but consistency between clinical symptoms and brain images changed depending on the clinical course. Initial abnormality waveforms on EEG markedly improved in accordance with recovery from hemiplegia, whereas cerebral blood flow on SPECT showed little improvement. Abnormality in the orbitofrontal cortex and hippocampus on MRI and SPECT corresponded to persistent brain dysfunctions, and both the symptoms and brain images had little change.
SK wrote the manuscript and takes responsibility for the contents of the article. RS provided support and supervision during clinical treatment and publication. This report was written using a regular medical record with no funding support. None of the authors has any conflicts of interest with regard to this article.