Advancement of the Cognitive Function on Laser Exposure after Tumor Removal in a Case with Brain Neoplasm

Cognition, the intellectual functions, is mental process of understanding through thought, experience, and the senses, and consists of attention, the formation of knowledge, memory and working memory, judgment and calculation, comprehension, problem solving and decision making [1]. Cognitive/mental disorders have been statistically measured as 15-20% of brain tumors, and can be the initial symptoms. The severity of cognitive deficits varies from attention to many conditions, for instance, delirium, dementia or amnesic syndrome. Cognitive disorders are strongly associated with several factors including the localization and nature of the tumor, peritumoral and remote alterations, and individual vulnerability [2]. Any brain tumor occurred in the exact or abutting area of cognition-related neural paths cause cognitive impairment. Cognitive deficits, especially memory, are the most common impairment after brain tumor [3]. 

There are many methods to treat brain tumor, such as surgical removal of tumor [4], chemotherapy [5], radiotherapy [6], rehabilitation [7] and others [8]. All of them tend to leave with cognitive deficits, especially people whose thalamus is impaired. Cognitive impairment, arising from tissue injury caused by the tumor itself, surgical resection and chemotherapy [9], is unsure and prevalent after operation for brain tumor [10]. 

Any novel method has been expecting to have a more fast recovery; therefore, the intravascular laser irradiation of blood (ILIB) comes with the tide of fashion. ILIB has been used in medical conditions, as its properties of increasing microcirculation and improving oxygen supply. It has been reported with efficacy in improving oxidative stress [11] and increased healing rate of wound [12]. 

We herein report a case with brain tumor with subsequent cognitive impairment, who was treated with ILIB and obtained better recovery of cognition.

Patient, a 43-year-old male, was robust in the past until the end of 2015. He experienced left lower limb weakness initially, which progressively developed poor ability to stand up when he woke up. There was neither numbness nor paresthesia in the beginning. He then felt difficulty in walking and stepping up the stairs Due to his worse weakness, he was introduced to our hospitalby transfer from local clinic. The results of the brain magnetic resonance (MR) imaging of brain was performed and disclosed a tumor (2.74 X 2.65 cm) located in the right subcortical peri-ventricular region abutting thalamus (Figure 1).

Figure 1: Brain MRI of our case before operation. This brain tumor shown as a high signal intensity on the area of the right peri-ventricular subcortical white matter in MRI T2 FLAIR image (A) which tumor abutting right thalamus. MRI T2 image, coronal view (B) MRI T2 image, sagittal view (C) MRI= magnetic resonance imaging.

He then underwent operation for craniectomy with tumor removal on January 28, 2016. According the description of Operative Note, after dissection of the skull by the neurosurgeon, the dura was opened to hinge on the edge of superior sagittal sinus and reflected medially, to avoid injury at the drainage vein originally directed to the superior sagittal sinus. The procedure of dissection of the arachnoid overlying the vein and freeing the vein from the underlying cortex provided added exposure. Application of self-retaining retractor pull the parieto-occipital lobe laterally, and the falx medially. The tumor as then removed delicately by tumor forces and micro-scissor under the microscopic maneuver. The dura was then closed and repaired. Patient was informed by the eminent surgeon as successful operation with nearly total (99.99%) removal of the entire tumor cells. The pathology confirmed it as diffuse astrocytoma (WHO grade II). Next day after operation, computer tomography (CT) of brain showed only post-operative edema around the operative area, and brain MRI checked 3 months later showed total absence of the brain tumor (Figure 2). Due to successful result of surgical resection of the brain tumor, the neurosurgeon did not endorse patient to receive chemotherapy and radiotherapy.

Figure 2: Radiographic films of brain after total removal of the brain tumor, one day (CT) and 3 months later (MRI). CT scan of brain one day after operation (A) MRI T2 image, axial view (B) MRI T2 FLAIR image, axial view (C) MRI T2 FLAIR image, sagittal view (D) CT = computed tomography, MRI= magnetic resonance imaging.

Right after the surgical operation, he cannot walk. According to the statement of the patient, his Left lower limb has no power but can drag his left lower limb to walk after ILIB. Though the numbness of the patient’s left side persists with hypesthesia, he still felt dramatic effect to move his left upper and lower limb with grade 3 muscles strength, which gradually improved from grade 1-2 to grade 3 after rehabilitation and ILIB. His left lower limb would tremor and be stiff when stretch and exertion, which usually happens on the patients who had impaired brain. He said, “I can walk with quad cane, but still cannot balance. The numbness on my face and left upper lower limb persists, but the sensation had improved a little bit not too obviously. I can feel the pain of injection while I could not feel the pain but numbness before.” At the last of conversation, the patient said that he has been under hot bath during the courses of ILIB, and he gets better effect. 

After operation, episode of left side weakness with hypoesthesia and numbness, including left face, was noted, so intensive rehabilitation was provided. After discharge, he came to our REH OPD on November 27, 2016 for help, where poor posture, weakness with grade 1-2 muscle strength, balance and disability of walk were discovered. The ADL assessment showed impaired, and the Barthel index scores were as follows: eating (10), grooming (10), dressing(5), balance(5), bathing(0), bladder management (0), bowel management(10), stairs(0), hygiene(0), ambulation(15), urination(10). The patient’s Mini-Mental State Examination (MMSE) scores were 12 (Figure 3).

Figure 3: MMSE of the case. ILIB, intravascular laser irradiation of blood.

Initially, he reported pain of left shoulder, left wrist, and right ankle joints for many months, and dragging leg in the left side became obvious while walking. He came to our OPD on September 12, 2018 again for further treatment. The brain regional perfusion with single-photon emission computed tomography (SPECT), one year far away from the date of operation, was checked in the first time, and showed diminished uptake in the right thalamus Figure 4A. 

We adopted the 632.8 nm wavelength helium-neon (HeNe) laser. The patient received three complete course of ILIB lasting an hour for 10 consecutive days. During the 3-course ILIB, patient reported no side effect, and felt his left upper lower limb range of motion improved. Although the numbness and burning-like sensation persisted, he could tolerate it without pain killers. He can now walk with quad cane with left anterior ankle-foot orthosis, even the gait pattern was still impaired with right foot vaulting and impaired balance. The patient’s memory was great before operation. After operation, his memory function decreased until the beginning of ILIB. The patient’s Mini-Mental State Examination (MMSE) scores were 29, better than 12 checked before Figure 3. Eight months later, the second brain SPECT showed improvement in some area as Figure 4B.

Figure 4: Regional perfusion SPECT before and after ILIB. The white to red area indicated better perfusion than the blue and green area. (A) This regional perfusion SPECT (conducted, after operation, before the patient underwent ILIB) shows the hypoperfusion on the right thalamus, where the color is blue and green. (B) The second regional perfusion SPECT (conducted after the patient underwent ILIB for 8 month, three ILIB courses) shows the improvement on the right thalamus, where the color turns red (arrowhead). SPECT, single-photon emission computed tomography. ILIB, intravascular laser irradiation of blood.

He has ever received 130 times of ILIB in our and other hospitals. Patient said that the amount of his white hair decreased, and the white-color hair was replaced with black hair, which makes him look younger after the courses of ILIB. The patient also stated that his metabolism has progressively improved due to ILIB. There were more times of urination than the time before using ILIB. In the past, he had few times of urination no matter how much water he drank. Thus, we took a look at his renal function examination report. Fortunately, although his eGFR decreased, his renal function did not show significant difference, as shown in Table 1.

Table 1: The table shows the patient’s renal function in 2016, 2017, and 2018.

The time interval of the whole clinical course, intervention, and associated evaluation was summarized in Figure 5.

Figure 5: Time interval of the case and his self-feeling.

In our case, the decreased perfusion of the right thalamus observed from the first SPECT improved significantly when compared with the second SPECT after 3-course ILIB. The improvement of the right thalamus shown in the second SPECT correlated with advancing the function of the cognition. 

Patients with brain tumors may suffer from cognitive deficits caused by the disease and/or its treatment. In a review article published in 2010, Gehring et al. [9] summarized the cognitive deficits in view of the broad domains of attention, language, memory, and executive functioning, and acclaimed potential causes for attribution as followed: 1) the tumor entity (location, size, progression and growth rate), 2) tumor-related neural complications and seizure, 3) radiation-related, early or late, with demyelination, leading to brain tissue inflammation/necrosis and impaired regeneration of hippocampal neurons; 4) antiepileptic drugs with subsequent endocrine/metabolic disturbances and psychological complication [9]. The cognitive impairment in our case should be highly related to tumor-related complication occurred in brain. 

In a neuropsychological study of brain tumor, Desmond [13] found cognitive deficits highly correlate with either the location or total volume of the white matter lesions, and recognized a stronger association between cognitive deficits and those lesions in executive function, most likely due to the involvement of frontal-sub-cortical pathways [13]. The reported prevalence rates of changes in personality and/or behavior varied from 8%-67% in glioma patients [14], Our case having the brain tumor abutting the thalamus was just in the area of white matter and the fact is compatible with Desmond’s finding. 

In order to address cognitive deficits in brain tumor survivors, some tailor-designing intervention programs including cognitive therapy and pharmacologic strategies, have found benefit [9]. On the other hand, we conducted ILIB for three courses, and patient appeared an obviously increased perfusion in the right thalamus, as well as the improved cognitive dysfunction, raising the realistic elucidation that improvement of thalamic perfusion and the cognition could be attributed to intervention of ILIB. 

According to the literature to date, ILIB is widely used in clinical treatment to improve a lot of poor prognostic, chronic painful or stroke-causing disease, for instance, diabetes mellitus [15-17] cardiovascular disorders [18], hepatology [19], obstetrics [20], and rheumatology [21-25] and stroke [26-28] as its properties of increasing microcirculation and improving oxygen supply. 

Cognitive impairment accounts for an important element of disability, and cognition has been demonstrated to be an independent predictor of survival in patients with cerebral neoplasms [29,30]. Our patient underwent 3 courses of ILIB, and his neural deficit including motor, sensation, memory and metabolism were gradually improved. A latest case report from our unit has approved that ILIB intervention can recuperate the cognitive impairment after stroke [27]. Cognition is strongly associated with function of thalamus, and in this case, the significant improvement of the patient’s right thalamus left with the better enhancement of the patient’s cognition, especially in his memory as he stated. 

Our case felt that his memory got improved after using ILIB. Memory was probably related to the thalamus as the first cognitive function [31]. Thalamus is one of the crucial elements of the Papez circuit, which is an important neural structure for integrating cognitive function [32]. One article of ours confirmed that the intervention of ILIB leads to the reversibility of cognitive dysfunction in adult with stroke, indicating recovery of brain parenchymal lesions related to post-stroke cognitive impairment was attributed by the intact of Papez circuit [27]. This deduction can be fit in our case. We believe that the benefit of ILIB can contribute to the increase of right thalamus. 

The fact of changing color of the patient’s hair from white to black is of interesting. ILIB is an alternative treatment for healing wound, relieving pain, promoting circulation and metabolism [15-17]. ILIB is able to induce a photobiological response inside the cells, activating the production of adenosine triphosphate (ATP), NO and reactive oxygen species, altering sodium-potassium pumps and calcium channels in cell membranes [33]. ILIB promote functional regeneration of mitochondria and pro-oxidant/ antioxidant equilibrium [11]. Furthermore, ILIB has been shown to alter ATP synthesis in white blood cells, as well as the deformation of red blood cells to pass through tiny blood vessels and amplify microcirculation [11], and to reduce low-density lipoprotein [11]. ILIB has been confirmed as biochemical modification of mitochondria and the activation of metabolic energy processes, which increases the production of ATP.

In conclusion, we deduce that the increase of hypoperfusion of right thalamus was attributed to ILIB, which might improve the cognitive function simultaneously. This is the first case to describe the relationship between the thalamic perfusion and cognitive function in brain tumor under ILIB. Based on the findings of SPECT and ensuing clinical presentation, we approve that the image is a very worthwhile instrument in the field of scintigraphic rehabilitation for the neurologic retrieval.