A 72-year-old woman with a middle school education who presented with headache, dizziness, nausea, and vomiting was admitted to a local hospital. In August 2021, she was diagnosed with tuberculous meningitis and underwent antituberculosis therapy. However, her symptoms did not disappear. After being discharged from the local hospital, she visited the neurology department of our hospital. CSF analysis and India ink staining of the CSF revealed Cryptococcus, and she was diagnosed with CM. She received antifungal therapy [fluconazole (10 mg/kg/day) and 5-fluorocytosine (100 mg/kg/day)] for almost 2 months before being affected by rapidly progressive dementia caused by central nervous system infection. On 25 November 2021, she began to show signs of confusion, an inability to speak, limited limb movements, an inability to walk, an inability to eat independently, signs of nausea without vomiting, and signs of incontinence, but she could still open her eyes when called and lacked limb convulsions. She was then hospitalized in our department. A lumbar puncture and CSF analysis were performed, which revealed an ICP of >200 mmH2O, a white blood cell (WBC) count of 7.4 cells/mul. a glucose level of 1.83 mmol/L, a protein level of 2,496 mg/L, and a chlorine level of 112.3 mmol/L. which suggested an inflammation. India ink staining of the CSF revealed Cryptococcus and CSF culture revealed Cryptococcus neoformans. Moreover, multiple intracranial lesions with meningeal enhancement were observed on brain magnetic resonance imaging (MRI; Figure 1). During hospitalization, the consciousness and mental state of the patient gradually improved after antifungal treatment with fluconazole and fluoropyrimidine, and cognitive function assessments revealed that the cognitive dysfunction of the patient persisted (Mini-Mental State Examination: 11 points, MoCA: 7 points); hence, the patient was referred to the Department of Rehabilitation Medicine for appropriate treatment while she demonstrated a weakness of the lower limbs and gait disturbance. After 2 weeks of receiving rTMS treatment, the condition of the patient was reevaluated, which revealed that all cognitive functions had significantly improved. The patient was conscious and responded slowly. Her ICP reached >200 mmH2O, and she had a WBC count of 11.83 cells/mul, a glucose level of 2.37 mmol/L, a protein level of 2,111 mg/L, and avchlorine level of 114.6 mmol/L. Additionally, the brain MRI images taken on 03 March 2022 revealed a significant reduction in the ventricles (MRI; Figure 2). Though the CSF culture was negative and cognitive function improved after rTMS therapy, we did not found a significant decline in inflammatory signals.
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Before rTMS treatment, the cognitive scale assessment results of the patient (Tables 1-3) indicated that the patient had severe cognitive impairment, and the MoCA assessment results revealed that the cognitive function of the patient was severely impaired; visuospatial and executive functions, object naming function, and abstract thinking function were severely reduced; and language function, short-term memory, and delayed recall function were impaired. The findings of the tests conducted using LOTCA and RBMT were identical in that the patients had a functional impairment and dysfunction in thinking operations, learning imitation, attention, and concentration. The scores on the aforementioned scales met the requirements for significant cognitive impairment.
The patient underwent a second evaluation of her cognitive performance after 2 weeks of rTMS treatment. The results showed that the cognitive function of the patient was greatly improved, and each subscore of the evaluation was very close to normal. The comprehensive analysis of assessment results and clinical observations revealed that the visuospatial function of the patient was significantly improved, and she could distinguish between her left and right limbs and identify the corresponding relationship between the front and the back and the left and the right of a picture. Meanwhile, the executive function, which includes drawing and imitating sketching, also improved. Time cognition and language function also significantly improved, and the patient could accurately express the current year, month, and season; tell the current time according to the clock; and name simple things. Furthermore, the memory function of the patient significantly improved; she was able to remember some basic phrases and complex routes and could execute simple recall tasks after a delay. However, the recall of complex tasks still required further improvement. In terms of learning and attention, the patient could learn how to use a calculator and imitate and copy graphics; in terms of logical thinking, the patient could classify simple objects and respond to straightforward logical questions.
Anti-infective therapy should be primarily addressed for the treatment of CM so that the cognitive impairments and other symptoms of the patients might be improved after controlling the infection. Additionally, rTMS therapy might improve the cognitive performance of the patient in different categories, including memory function, time perception, visuospatial cognition, speech, and executive function. This case provides a novel treatment method for patients with CM in conjunction with cognitive impairment, and our findings serve as a foundation for future clinical investigations. However, it is essential to increase the patient sample size to conduct a thorough analysis because of the limitations of case studies on individual differences. Finally, further exploration and research could be conducted on the selection of precise stimulation targets and stimulation parameters in rTMS, as well as analysis combined with imaging examinations, neurophysiology, and other clinical techniques.