Open Brain Surgery Research Articles

High-precision stereotactic irradiation for focal drug-resistant epilepsy versus standard treatment: a randomized waitlist-controlled trial (the PRECISION trial)

IntroductionThe standard treatment for patients with focal drug-resistant epilepsy (DRE) who are not eligible for open brain surgery is the continuation of anti-seizure medication (ASM) and neuromodulation. This treatment does not cure epilepsy but only decreases severity. The PRECISION trial offers a non-invasive, possibly curative intervention for these patients, which consist of a single stereotactic radiotherapy (SRT) treatment. Previous studies have shown promising results of SRT in this patient population. Nevertheless, this intervention is not yet available and reimbursed in the Netherlands. We hypothesize that: SRT is a superior treatment option compared to palliative standard of care, for patients with focal DRE, not eligible for open surgery, resulting in a higher reduction of seizure frequency (with 50% of the patients reaching a 75% seizure frequency reduction at 2 years follow-up).MethodsIn this waitlist-controlled phase 3 clinical trial, participants are randomly assigned in a 1:1 ratio to either receive SRT as the intervention, while the standard treatments consist of ASM continuation and neuromodulation. After 2-year follow-up, patients randomized for the standard treatment (waitlist-control group) are offered SRT. Patients aged ≥ 18 years with focal DRE and a pretreatment defined epileptogenic zone (EZ) not eligible for open surgery will be included. The intervention is a LINAC-based single fraction (24 Gy) SRT treatment. The target volume is defined as the epileptogenic zone (EZ) on all (non) invasive examinations. The seizure frequency will be monitored on a daily basis using an electronic diary and an automatic seizure detection system during the night. Potential side effects are evaluated using advanced MRI, cognitive evaluation, Common Toxicity Criteria, and patient-reported outcome questionnaires. In addition, the cost-effectiveness of the SRT treatment will be evaluated.DiscussionThis is the first randomized trial comparing SRT with standard of care in patients with DRE, non-eligible for open surgery. The primary objective is to determine whether SRT significantly reduces the seizure frequency 2 years after treatment. The results of this trial can influence the current clinical practice and medical cost reimbursement in the Netherlands for patients with focal DRE who are not eligible for open surgery, providing a non-invasive curative treatment option.Trial registrationClinicaltrials.gov Identifier: NCT05182437. Registered on September 27, 2021.

Radiation necrosis after radiation therapy treatment of brain metastases: A computational approach.

Metastasis is the process through which cancer cells break away from a primary tumor, travel through the blood or lymph system, and form new tumors in distant tissues. One of the preferred sites for metastatic dissemination is the brain, affecting more than 20% of all cancer patients. This figure is increasing steadily due to improvements in treatments of primary tumors. Stereotactic radiosurgery (SRS) is one of the main treatment options for patients with a small or moderate number of brain metastases (BMs). A frequent adverse event of SRS is radiation necrosis (RN), an inflammatory condition caused by late normal tissue cell death. A major diagnostic problem is that RNs are difficult to distinguish from BM recurrences, due to their similarities on standard magnetic resonance images (MRIs). However, this distinction is key to choosing the best therapeutic approach since RNs resolve often without further interventions, while relapsing BMs may require open brain surgery. Recent research has shown that RNs have a faster growth dynamics than recurrent BMs, providing a way to differentiate the two entities, but no mechanistic explanation has been provided for those observations. In this study, computational frameworks were developed based on mathematical models of increasing complexity, providing mechanistic explanations for the differential growth dynamics of BMs relapse versus RN events and explaining the observed clinical phenomenology. Simulated tumor relapses were found to have growth exponents substantially smaller than the group in which there was inflammation due to damage induced by SRS to normal brain tissue adjacent to the BMs, thus leading to RN. ROC curves with the synthetic data had an optimal threshold that maximized the sensitivity and specificity values for a growth exponent β* = 1.05, very close to that observed in patient datasets.

Laser interstitial thermal therapy in pediatric cerebellar epilepsy.

Cerebellar lesional epilepsy is rare, commonly manifesting in early life and posing diagnostic and treatment challenges. Seizure semiology may be subtle, with repetitive eye blinking, face twitching, and irregular breathing, while EEG commonly remains unremarkable. Pharmacoresistance is the rule, and surgical intervention is the only treatment with the potential for cure. Novel minimally invasive techniques, such as laser interstitial thermal therapy (LITT), are emerging for surgically less accessible, deep-seated epileptogenic lesions. We report the case of a patient who presented with peculiar eye and face movements occurring episodically and stereotypically since the first weeks of life and was later diagnosed with cerebellar epilepsy related to a hamartoma. Refractory daily seizures, unresponsive to antiseizure medication, were followed by increasingly prominent gait ataxia and delayed speech development. Staged LITT was performed in two consecutive sessions at 3 and 4 years, leading to seizure cessation, neurological improvement, and developmental gains over a postsurgical follow-up period of 8 months. Our case highlights cerebellar lesional epilepsy as a rare but important differential diagnosis in children with paroxysmal disorders predominantly involving the face. Furthermore, we illustrate the radiological correlates of neurocognitive deficit related to the cerebellar lesion, manifesting as cerebello-cerebral diaschisis. Most importantly, our observations showcase LITT as a safe and effective therapeutic approach in cerebellar lesional epilepsy and an attractive alternative to open brain surgery, especially for deep-seated lesions in the pediatric population.

Assessment of Safety of a Fully Implanted Endovascular Brain-Computer Interface for Severe Paralysis in 4 Patients

Brain-computer interface (BCI) implants have previously required craniotomy to deliver penetrating or surface electrodes to the brain. Whether a minimally invasive endovascular technique to deliver recording electrodes through the jugular vein to superior sagittal sinus is safe and feasible is unknown. To assess the safety of an endovascular BCI and feasibility of using the system to control a computer by thought. The Stentrode With Thought-Controlled Digital Switch (SWITCH) study, a single-center, prospective, first in-human study, evaluated 5 patients with severe bilateral upper-limb paralysis, with a follow-up of 12 months. From a referred sample, 4 patients with amyotrophic lateral sclerosis and 1 with primary lateral sclerosis met inclusion criteria and were enrolled in the study. Surgical procedures and follow-up visits were performed at the Royal Melbourne Hospital, Parkville, Australia. Training sessions were performed at patients' homes and at a university clinic. The study start date was May 27, 2019, and final follow-up was completed January 9, 2022. Recording devices were delivered via catheter and connected to subcutaneous electronic units. Devices communicated wirelessly to an external device for personal computer control. The primary safety end point was device-related serious adverse events resulting in death or permanent increased disability. Secondary end points were blood vessel occlusion and device migration. Exploratory end points were signal fidelity and stability over 12 months, number of distinct commands created by neuronal activity, and use of system for digital device control. Of 4 patients included in analyses, all were male, and the mean (SD) age was 61 (17) years. Patients with preserved motor cortex activity and suitable venous anatomy were implanted. Each completed 12-month follow-up with no serious adverse events and no vessel occlusion or device migration. Mean (SD) signal bandwidth was 233 (16) Hz and was stable throughout study in all 4 patients (SD range across all sessions, 7-32 Hz). At least 5 attempted movement types were decoded offline, and each patient successfully controlled a computer with the BCI. Endovascular access to the sensorimotor cortex is an alternative to placing BCI electrodes in or on the dura by open-brain surgery. These final safety and feasibility data from the first in-human SWITCH study indicate that it is possible to record neural signals from a blood vessel. The favorable safety profile could promote wider and more rapid translation of BCI to people with paralysis. ClinicalTrials.gov Identifier: NCT03834857.

PCR54 Patient Preferences for Treatment Alternatives for Drug-Resistant Epilepsy

For a subset of patients with drug-resistant focal epilepsy, surgery offer a substantial chance for seizure freedom. Laser interstitial thermal therapy (LITT) is a minimally invasive approach for tissue ablation using thermotherapy, but may offer a lower chance of seizure freedom. The objective was to quantify the minimum chance of seizure freedom with LITT that patients would accept to avoid open brain surgery.

Patient preferences pertaining to treatment options for drug-resistant focal epilepsy

ObjectiveTo determine patient acceptability of benefit-risk trade-offs in selecting treatment options for drug-resistant mesial temporal lobe epilepsy, including open brain surgery, laser ablation (laser interstitial thermal therapy [LITT]), and continued medications. MethodsA discrete-choice experiment survey was developed, consisting of 20 versions that were randomly assigned to respondents. Each version had 8 sets of constructed treatment alternatives, representing open brain surgery, LITT, or continued medical management. For each set, respondents indicated the treatment alternative they would choose first. Treatment alternatives were characterized by varying levels of chance of seizure freedom for at least 2 years (20–70%), risk of 30-day mortality (0–10%), and risk of neurological deficits (0–40%). Respondents’ choices were analyzed using random-parameters logit models to quantify acceptable benefit-risk trade-offs. Preference heterogeneity was evaluated using latent-class analysis. ResultsThe survey was administered to 2 cohorts of adult patients with drug-resistant epilepsy: a Duke cohort identified using diagnostic codes (n = 106) and a web-recruited panel with a self-reported physician diagnosis of drug-resistant epilepsy (n = 300). Based on mean preference weights, respondents who indicated a willingness to consider surgical intervention would accept a reduction in chance of seizure freedom from 70% to a minimum-acceptable benefit (MAB) of 23% if they could undergo LITT rather than open brain surgery. For a reduction in 30-day mortality from 1% to 0%, MAB was 52%. For a reduction in risk of long-term deficits from 10% to 0%, MAB was 39%. Latent-class analysis revealed additional choice patterns identifying respondent groups that more strongly favored continuing medications or undergoing surgery. ConclusionPatients who are receptive to surgery would accept significantly lower treatment effectiveness to undergo a minimally invasive procedure relative to open brain surgery. They also were willing to accept lower treatment benefit to reduce risks of mortality or neurological deficits.

Current applications and safety profile of laser interstitial thermal therapy in the pediatric population: a systematic review of the literature.

Laser interstitial thermal therapy (LITT) provides a minimally invasive alternative to open brain surgery, making it a powerful neurosurgical tool especially in pediatric patients. This systematic review aimed to highlight the indications and complications of LITT in the pediatric population. In line with the PRISMA guidelines, the authors conducted a systematic review to summarize the current applications and safety profiles of LITT in pediatrics. PubMed and Embase were searched for studies that reported the outcomes of LITT in patients < 21 years of age. Retrospective studies, case series, and case reports were included. Two authors independently screened the articles by title and abstract followed by full text. Relevant variables were extracted from studies that met final eligibility, and results were pooled using descriptive statistics. The selection process captured 303 pediatric LITT procedures across 35 studies. Males comprised approximately 60% of the aggregate sample, with a mean age of 10.5 years (range 0.5-21 years). The LITT technologies used included Visualase (89%), NeuroBlate (9%), and Multilase 2100 (2%). The most common indication was treatment of seizures (86%), followed by brain tumors (16%). The mean follow-up duration was 15.6 months (range 1.3-48 months). The overall complication rate was 15.8%, which comprised transient neurological deficits, cognitive and electrolyte disturbances, hemorrhage, edema, and hydrocephalus. No deaths were reported. As of now, LITT's most common applications in pediatrics are focused on treating medically refractory epilepsy and brain tumors that can be difficult to resect. The safety of LITT can provide an attractive alternative to open brain surgery in the pediatric population.

The Role of Focused Ultrasound in the Management of Movement Disorders: Insights after 5 Years of Experience.

The Role of Focused Ultrasound in the Management of Movement Disorders: Insights after 5 Years of Experience.

Intraoperative Imaging of Cortical Blood Flow by Camera-Based Photoplethysmography at Green Light

Intraoperative evaluation of blood perfusion in the brain cortex is an important but hitherto unresolved problem. Our aim was to demonstrate the feasibility of cerebral microcirculation assessment during open brain surgery by using camera-based photoplethysmography (cbPPG) synchronized with an electrocardiograph. Cortical blood flow was monitored in five patients with different diagnoses. Two cases (tumor resection and extra-intracranial bypass grafting) are presented in detail. Blood-flow parameters were visualized after processing cortex images recorded under green-light illumination before and after surgical intervention. In all cases, blood flow was successfully visualized in &gt;95% of open brain. Distributions of blood pulsation amplitude, a parameter related to cortical blood perfusion; pulse arrival time; and blood-pressure-pulse shape were calculated with high spatial resolution (in every pixel). Changes in cerebral blood supply caused by surgical intervention were clearly revealed. We have shown that the temporal spread of pulse arrival time and the spatiotemporal variability of pulse shape are very sensitive markers of brain circulatory disturbances. The green-light cbPPG system offers a new approach to objective assessment of blood-flow changes in the brain during surgical intervention. The proposed system allows for contactless monitoring of cortex blood flow in real time with high resolution, thus providing useful information for surgery optimization and minimization of brain tissue damage.

Retrospective Chronologic Computed Tomography Analysis of Bone Flap Fusion and Resorption After Craniotomy and Autologous Cryopreserved Cranioplasty

In open brain surgery, fixation of the bone flap is the final procedure. The bone flaps then fuse naturally. The objective of this study was to investigate the chronological process of bone fusion after craniotomy and autologous cranioplasty. Retrospective data were collected from patients who underwent craniotomy or cranioplasty after August 2004 and had at least 1 computed tomography (CT) scan at 3 months postsurgery. The patients were divided into a craniotomy group and a cranioplasty group. Head CT scans were analyzed to evaluate bone fusion and resorption. Records from 978 patients who underwent craniotomy or cranioplasty between September 2004 and November 2015 were reviewed; 369 patients were eligible for the final analysis (craniotomy, n= 276; cranioplasty, n= 93). The mean cryopreservation period for the bone flap in the cranioplasty group was 49.3 days. The mean patient age was 51.4 ± 18.1 years in the craniotomy group and 51.6 ± 17.1 years in the cranioplasty group. Head CT scans showed bone fusion rates of 76.6% in the craniotomy group and 53.3% in the cranioplasty group at 6 months postsurgery (P= 0.015) and 78.6% and 78.1%, respectively, at 1 year postsurgery (P= 0.951). There was also a significant difference in the bone flap resorption rate between the 2 groups. Bone flap fusion rates after craniotomy and cranioplasty were significantly different before 12 months, but not significantly different thereafter. Bone resorption occurred more frequently in the cranioplasty group over time.

Removing the Need for Invasive Brain Surgery: The Potential of Stent Electrodes

Over the last decade, significant advances in brain–machine interfaces have demonstrated that people with paralysis can control assistive technology such as computers, wheelchairs and bionic arms with their minds. However, due to the invasive surgery required to access the brain and implant electrodes, to date, no device has received commercial US FDA approval, and consequently there is no existing solution to return independence and mobility for the hundreds-of-millions of people paralyzed by stroke, spinal cord injury and motor neuron disease. But there is hope. We have developed a minimally invasive brain–machine interface that can access the brain using cortical vessels which mitigates the risks associated with open brain surgery.

Effect of Implant Duration, Anatomical Location and Electrode Orientation on Bandwidth Recorded with a Chronically Implanted Endovascular Stent-Electrode Array.

Access to the brain to implant recording electrodes has conventionally required a craniotomy. To mitigate risks of open brain surgery, we previously developed a stent-electrode array that can be delivered to the cortex via cerebral vessels. Following implantation of a stent-electrode array (Stentrode) in a large animal model, we investigated the longevity of highquality signals, by measuring bandwidth in animals implanted for up to six months; no signal degradation was observed. We also investigated whether bandwidth was influenced by implant location with respect to the superior sagittal sinus and branching cortical veins; it was not. Finally, we assessed whether electrode orientation had an impact on recording quality. There was no significant difference in bandwidths from electrodes facing different orientations. Interestingly, electrodes facing the skull (180°) were still able to record neural information with high fidelity. Consequently, a minimally invasive surgical approach combined with a stent-electrode array is a safe and efficacious technique to acquire neural signals over a chronic duration.

Focused ultrasound ablation as tremor treatment

The development of high-intensity magnetic resonance imaging (MRI)-guided focused ultrasound (MRIgFUS) ablation has widened the spectrum of interventional techniques for stereotactic functional neurosurgery of lesions. This has resulted in novel incisionless intervention approaches for the therapy of tremor disorders. The safety and efficacy is documented by recent study data. This article encompasses adescription of the technological basis and typical course of MRIgFUS interventions, acomparison to alternative open or incisionless surgical techniques as well as areview of the current evidence base for MRIgFUS ablation in the context of lesional interventions to treat tremor. Narrative literature review and comparison. Depending on the surgical target and tremor etiology published trials of MRIgFUS ablation report areduction of tremor intensity of up to 80% after 6-12months follow-up without the disadvantages of open brain surgery. The MRIgFUS functional neurosurgery is conducted only at alimited number of treatment sites. First data on lesions of the thalamic ventral intermediary nucleus (V.im.) as well as subthalamic fiber tracts have been published. These results indicate an effective and safe treatment of tremor disorders by MRIgFUS ablation. Incisionless lesional surgery using MRIgFUS is asignificant addition to the interventional armamentarium for functional stereotactic neurosurgery and apotentially valuable alternative to established interventional therapy options for tremor disorders.

How I do it: Awake craniotomy.

Awake craniotomy allows continuous assessment of a patient's clinical and neurological status during open brain surgery. This facilitates early detection of interference with eloquent cortex, and hence can allow a surgeon to maximize resection margins without compromising neurological function. Awake craniotomy requires an effective scalp blockade, intraoperative assessment, and a carefully co-ordinated theatre team. A variety of clinical and electrophysiological techniques can be used to assess cortical function. Effective scalp blockade and awake craniotomy provides the opportunity to intraoperatively assess cortical function in the awake patient, thus providing an important neurosurgical option for lesions near eloquent cortex.

Intraoperative Probe-Based Confocal Laser Endomicroscopy in Surgery and Stereotactic Biopsy of Low-Grade and High-Grade Gliomas: A Feasibility Study in Humans.

The management of gliomas is based on precise histologic diagnosis. The tumor tissue can be obtained during open surgery or via stereotactic biopsy. Intraoperative tissue imaging could substantially improve biopsy precision and, ultimately, the extent of resection. To show the feasibility of intraoperative in vivo probe-based confocal laser endomicroscopy (pCLE) in surgery and biopsy of gliomas. In our prospective observational study, 9 adult patients were enrolled between September 2014 and January 2015. Two contrast agents were used: 5-aminolevulinic acid (3 cases) or intravenous fluorescein (6 cases). Intraoperative imaging was performed with the Cellvizio system (Mauna Kea Technologies, Paris). A 0.85-mm probe was used for stereotactic procedures, with the biopsy needle modified to have a distal opening. During open brain surgery, a 2.36-mm probe was used. Each series corresponds to a separate histologic fragment. The diagnoses of the lesions were glioblastoma (4 cases), low-grade glioma (2), grade III oligoastrocytoma (2), and lymphoma (1). Autofluorescence of neurons in cortex was observed. Cellvizio images enabled differentiation of healthy "normal" tissue from pathological tissue in open surgery and stereotactic biopsy using fluorescein. 5-Aminolevulinic acid confocal patterns were difficult to establish. No intraoperative complications related to pCLE or to use of either contrast agent were observed. We report the initial feasibility and safety of intraoperative pCLE during primary brain tumor resection and stereotactic biopsy procedures. Pending further investigation, pCLE of brain tissue could be utilized for intraoperative surgical guidance, improvement in brain biopsy yield, and optimization of glioma resection via analysis of tumor margins. 5-ALA, 5-aminolevulinic acidpCLE, probe-based confocal laser endomicroscopyPpIX, protoporphyrin IX.

A Case of Recurrent Acromegaly: Medical Management of the Disease

Introduction: Acromegaly is a rare, chronic, insidious disease characterized by overproduction of growth hormone (GH) and its tissue mediator insulin-like growth factor 1 (IGF-1) typically from a pituitary adenoma. Recurrent acromegaly is established by GH hypersecretion after initial biochemical cure, and is even rarer than the disease itself, reported in only 2 to 3% of the cases. Case Report: We present a case of a 44 year-old Hispanic male with a past medical history of acromegaly diagnosed 20 years ago initially treated with transsphenoidal microsurgery and open brain surgery two years after the first procedure. He was lost to follow up and presented to our outpatient clinic 18 years later complaining of frequent headaches with nose and hands enlargement. Physical examination revealed an overweight male patient with a height of 75 inches, enlarged nose, lips, splayed teeth, coarse facial features, macroglossia, and enlargement of both hands with hyperhidrosis of his palms. Laboratory work up confirmed the diagnosis of recurrent acromegaly with elevated fasting IGF-1 level. MRI of the brain showed a 4.3 x 3.8cm pituitary macroadenoma with extensive suprasellar extension and optic chiasm compression. Medical treatment with Octreotide Long-Acting Release (LAR) was started immediately and subsequent repeat IGF-1 levels have shown progressive improvement. Discussion: This patient’s case of recurrent acromegaly shows the importance of follow up after any surgical or medical intervention in acromegaly patients. Recurrence, though infrequent, is possible and these patients have been identified as a subset of patients that can be difficult to manage. Therefore close monitoring with IGF-1 and GH levels is crucial to diagnose and treat recurrence of the disease and its comorbidities. Our goal was to achieve a biochemical cure, however given the fact that the patient refused any surgical intervention, makes the case even harder to manage. Somatostatin analogues have proven to be effective in cases like ours, yet its efficacy varies among studies.

Relationship between perioperative blood transfusion and post-operative hospital infection in patients with closed traumatic brain injury

To explore the relationship between allogeneic transfusion and hospital infections in patients with closed traumatic brain injury in the perioperative period. The clinical data of 181 patients with open brain surgery suffering closed brain injury in Changsha Central Hospital from February, 2012 to December, 2013 were retrospectively collected. The patients were divided into a mild and moderate brain injury group (n=83) and a severe brain injury group (n=98) according to evaluation system of Glasgow coma scale (GCS). They were also divided into a autologous transfusion plus mild and moderate brain injury group (n=14), a autologous transfusion plus severe brain injury group (n=10); an allogeneic transfusion plus mild and moderate brain injury group (n=31), an allogeneic transfustion plus severe brain injury group (n=70); a non-transfusion plus mild and moderate brain injury group (n=38) and a non-transfusion plus severe brain injury group (n=18) according to the transfusion styles. The hospital infection of all the patients was examined. The rate of hospital infection was significantly higher in the severe brain injury group than that in the mild and moderate brain injury group (P<0.05). The rate of post-operative hospital infection in the allogeneic transfusion plus severe brain injury group was also significantly higher than that in the autologous transfusion plus severe brain injury group (P<0.05). Similarly, the rate of post-operative hospital infection in the allogeneic transfusion plus mild and moderate brain injury group is higher than that in the non-transfusion plus mild and moderate brain injury group (P<0.05). The allogeneic transfusion at perioperative period may be one of the risk factors for post-operative hospital infection in the closed brain injury patients. The more severe the injury is, the higher risk the hospital infection will be.

The Epidemiology of Pediatric Open Brain Surgery in the United States. (P4.329)

The Epidemiology of Pediatric Open Brain Surgery in the United States. (P4.329)

Comparative analysis of dural reconstruction methods in open brain surgery for prevention of postoperative cerebrospinal fluid leakage

Aim. A comparative evaluation of dural reconstruction results using different material: patient’s own tissues (periosteal fragments, m. temporalis fascia or fascia lata), dural graft implants, collagen matrix, as well as evaluation of adhesive compositions effect for dural sutures sealing. Methods. Results of different types of dural reconstruction used in 243 patients operated between 2009 and 2012 were analyzed. Additional materials were required to complete dural reconstruction in 91 cases. Three patient groups were formed depending on the type of plastic material: patient’s own tissues, artificial materials and collagen matrix without suture fixation. In first two groups, sutures fixed plastic material, adhesive compositions or collagen materials were used as sealant in some cases. Effect in postoperative cerebrospinal fluid leakage preventing was assessed for different plastic materials, as well as for additional dural sealants. Results. Cerebrospinal fluid leakage frequency was similar (p 0.05) regardless of the type of plactic material (patient’s own tissues, dural graft implants, collagen matrix) use and was assessed as 26.2, 29.0 and 27.8% accordingly. In subgroups where sutures between dura mater and graft were additionally strengthened by adhesive compositions or collagen stripes, cerebrospinal fluid leakage rate (23.3%) was lower (p 0.05) compared to subgroups without sealant (44.4%). Conclusion. The type of plastic material does not matter for effective cerebrospinal fluid leakage prevention. Additional sealing of recovered dura mater reduces the risk of postoperative cerebrospinal fluid leakage.

Photobleaching-Insensitive Fluorescence Diagnostics in Skin and Brain Tissue

In this paper, we investigate the possibility of using accurate prediction models for the prediction of protoporphyrin bleaching dynamics to achieve photobleaching-insensitive methods to improve the evaluation of data in an existing clinical fluorescence-guided resection technique. To simulate the scenario, measurements were carried out in vivo on skin of healthy volunteers using a compact fiber-based fluorescence spectroscopy system. We have developed an effective method for the parameterization of sequences of bleaching spectra. We analyze convergence and decay rates with respect to initial conditions and excitation irradiance. We also discuss the consequences and the potential for bleaching-insensitive measurements and their applicability in a few examples from in vivo open brain surgery.