Delayed post-hypoxic parkinsonism with leukoencephalopathy associated with carbon monoxide poisoning

Dear Editor, Delayed post-hypoxic leukoencephalopathy is a rare disorder that occurs following any event that causes prolonged cerebral hypo-oxygenation.[1] The earliest cases of this condition were associated with carbon monoxide (CO) exposure, which continues to be the most common inciting agent.[2] However, delayed post-hypoxic leukoencephalopathy is also associated with cardiac arrest, strangulation, anesthetic or surgical complications, benzodiazepine or opiate overdose, and hemorrhagic shock.[3-7] Although its exact incidence is unknown, it is likely to increase due to the decreased fatality rate resulting from improved medical care of the aforementioned causes; for example, the mortality rate with CO poisoning has decreased from 33% to 3% since the early 19th century.[8] Delayed post-hypoxic leukoencephalopathy characteristically presents in two phases: altered sensorium followed by complete recovery and a subsequent acute-onset neuropsychiatric syndrome with or without associated features such as parkinsonism, mutism, hyperreflexia, and frontal release signs. The lucid interval typically lasts 1–3 weeks (with a range of 2–40 days).[2] Magnetic resonance imaging (MRI) of the brain reveals diffuse symmetrical anterior predominant cerebral white matter demyelination. A typical history with MRI findings that exclude alternative possibilities is sufficient for diagnosis. Early diagnosis is crucial to prevent unnecessary and unwarranted investigations and treatment. We present a case of delayed post-hypoxic parkinsonism and leukoencephalopathy following CO poisoning to emphasize the importance of early diagnosis. A 39-year-old man, with no prior comorbidities or addictions, was discovered unconscious in his room by his brother. The patient had not experienced any previous symptoms of fever, headache, or seizures but had slept in his room with burning logs of coal for warmth the previous night. He was taken to a nearby hospital, where he received a Glasgow coma scale score of E3V1M5 (9/15) and was intubated for airway protection. There were no signs of meningeal involvement. Magnetic resonance imaging (MRI) of the brain revealed nonspecific changes [Figure 1], and his cerebrospinal fluid examination and routine investigations were within normal ranges. He was treated with high-flow oxygen and showed improvement over the next five days, following which he was extubated. He gradually regained near baseline status and was discharged after ten days. However, one week after his discharge, he developed a sudden onset of worsening behavioral symptoms (aggression and verbal abuse), generalized stiffness, and slowed activities (required more time to do tasks such as washing, eating, and conducting daily living activities). He also exhibited intellectual abnormalities (inability to understand spoken words, producing incomprehensible sounds, and forgetfulness regarding navigating around the house). Therefore, he was referred to our facility for further management. Upon examination, he appeared drowsy with mask-like facies and displayed cog-wheel rigidity, bradykinesia, and hyperreflexia in all limbs (without asymmetry). He did not exhibit tremors, his extra-ocular movements were normal, and he did not experience postural instability. A detailed cognitive and sensory assessment was not possible, and he did not present with any focal neurological deficits.Figure 1: Axial T2-WI (a, c) images show nonspecific multiple hyperintense foci in the deep frontal white matter (arrows in a) and bilateral centrum semiovale (c). These lesions are hyperintense on DWI (arrows in b and d) without any diffusion restriction in the ADC maps (not shown)The routine blood investigations were normal. The MRI brain revealed widespread bilateral white matter hyperintensities, without any restriction in diffusion and with patchy contrast enhancement [Figure 2]. Cerebrospinal fluid (CSF) examination revealed a slightly increased protein level (83 mg/dl) with no presence of cells and normal sugar levels. Viral markers for HIV, hepatitis B and C, serum and CSF autoimmune and paraneoplastic panel, extractable nuclear antigen panel, blood and urine toxicology screen, and CSF-venereal disease research laboratory all yielded negative results. The electroencephalogram revealed a diffuse delta slowing of brain waves.Figure 2: Follow-up MRI displays diffuse confluent symmetrical white matter hyperintensity T2-WI (a, b) and diffusion-weighted images (c, d) without any diffusion restriction in the ADC maps (e, f). Multiple foci of hyperintensities (arrows in b) are observed within the bilateral centrum semiovale, Following gadolinium administration, no enhancement is seen except for a few enhancing foci in the left centrum semiovaleBased on the patient’s clinical presentation and the results of the investigations, a diagnosis of delayed post-hypoxic neurological deterioration was established. The patient was managed conservatively with the administration of atypical antipsychotics (quetiapine), levodopa-carbidopa, and baclofen. He continued to improve gradually and approached the baseline status over 6 months. Our patient developed delayed post-hypoxic neurological deterioration caused by CO poisoning resulting from sleeping in a closed room with biofuel combustion. CO binds tightly and preferentially to hemoglobin, thereby preventing oxygen binding and causing anemic hypoxia.[1] In addition, it inhibits cytochrome oxidase activity, inhibiting aerobic respiration.[1] Hypo-oxygenation and associated energy depletion of cerebral white matter lead to delayed apoptosis of oligodendrocytes due to glutamate-induced excitotoxicity.[9] CO poisoning can also occur from the use of gas geysers in domestic settings.[10] Correia et al.[10] reported cases of 26 patients developing unexplained neurodeficits while bathing in ill-ventilated bathrooms with gas geysers. Thirteen of these patients presented with acute CO intoxication, and two of them later developed parkinsonian features. Lee and Marsden reported cases of delayed post-hypoxic neurological manifestations as typically conforming to either parkinsonism or akinetic mutism along with the neuro-behavioral syndrome.[11] The patients who develop parkinsonism develop varying combinations of short-steppage gait, decreased arm swing, rigidity, bradykinesia, mask-like facies, and a stooped posture.[11] Certain patients even develop concomitant dystonic posturing of the limbs. Approximately 60% of the patients improve with supportive treatment and recover independent ambulation within 10–148 days after sequelae onset.[11] In our case, the patient had developed typical parkinsonian features (i.e., rigidity, bradykinesia, mask-like facies with hypokinetic dysarthria) and responded well to conservative management with levodopa and low doses of antipsychotics. The patient recovered his baseline status at the 6-month follow-up visit. Alternative diagnoses were ruled out through imaging, blood tests, and CSF testing. The prompt diagnosis and treatment prevented unnecessary resource utilization, such as brain biopsy or other invasive procedures, and provided symptomatic relief. Acknowledgment None. Author contribution Research project Conception: BP, AA, DG, AKS Organization: BP, AA, DG, AG, AKP, DMR, AKS Execution: BP, AA, DG, AG, AKP, DMR, AKS Statistical analysis Design: BP, AA, DG, AG, AKP, DMR, AKS Execution: BP, AA, DG, AG, AKP, DMR, AKS Review and Critique: BP, AA, DG, AG, AKP, DMR, AKS Manuscript preparation Writing of the first draft: BP, AA, DG, AKS Review and Critique: BP, AA, DG, AG, AKP, DMR, AKS Ethical compliance statement The authors confirm that they have read the Journal’s position on issues involved in ethical publication and affirm that this work is consistent with those guidelines. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.