Anesthetic management of a patient with Sturge-Weber syndrome in sagittal split ramus osteotomy surgery.

Sturge-Weber syndrome (SWS) is a neurocutaneous syndrome characterized by angiomas. This report presents airway management using submental intubation in sagittal split ramus osteotomy under general anesthesia and aimed to explore better anesthetic management for avoiding the rupture of angiomas in a patient with SWS.

Severe perioperative lactic acidosis in a pediatric patient with glycogen storage disease type Ia: a case report.

BACKGROUND: Glycogen storage disease (GSD) is a group of rare inherited metabolic disorders caused by enzyme deficiencies in glycogen catabolism. GSD type Ia is a congenital deficiency of the enzyme responsible for the final step in glucose production by glycolysis, resulting in impaired carbohydrate metabolism. CASE PRESENTATION: A 14-year-old boy with GSD type Ia was scheduled for a maxillary cystectomy under general anesthesia. He was taking oral sugars such as uncooked cornstarch regularly to prevent hypoglycemia. Perioperatively, glucose was administered via the peripheral vein for fasting; however, severe lactic acidosis occurred. He also developed hypercapnia because of intraoperative poor ventilation caused by hepatomegaly. CONCLUSIONS: We experienced a child with GSD type Ia who developed severe lactic acidosis despite continuous glucose infusion. Further studies are required to determine appropriate perioperative management for patients with GSD, including fasting glucose administration.

Usefulness of new acoustic respiratory sound monitoring with artificial intelligence for upper airway assessment in obese patients during monitored anesthesia care.

Monitored anesthesia care (MAC) often causes airway complications, particularly posing an elevated risk of aspiration and airway obstruction in obese patients. This study aimed to quantify the levels of aspiration and airway obstruction using an artificial intelligence (AI)-based acoustic analysis algorithm, assessing its utility in identifying airway complications in obese patients. To verify the correlation between the stridor quantitative value (STQV) calculated by acoustic analysis and body weight, and to further evaluate fluid retention and airway obstruction, STQV calculated exhaled breath sounds collected at the neck region, was compared before and after injection of 3 ml of water in the oral cavity and at the start and end of the MAC procedures. STQV measured immediately following the initiation of MAC exhibited a weak correlation with body mass index. Furhtermore, STQV values before and after water injection increased predominantly after injection, further increased at the end of MAC. AI-based analysis of cervical respiratory sounds can enhance the safety of airway management during MAC by quantifying airway obstruction and fluid retention in obese patients. J. Med. Invest. 70 : 430-435, August, 2023.

Efficacy and safety of remimazolam besilate for sedation in outpatients undergoing impacted third molar extraction: a prospective exploratory study.

BACKGROUND: Dental treatments often cause anxiety, fear, and stress in patients. Intravenous sedation is widely used to alleviate these concerns, and various agents are employed for sedation. However, it is important to find safer and more effective sedation agents, considering the adverse effects associated with current agents. This study aimed to investigate the efficacy and safety of remimazolam besilate (hereinafter called "remimazolam") and to determine the optimal dosages for sedation in outpatients undergoing dental procedures. METHODS: Thirty-one outpatients aged 18-65 years scheduled for impacted third molar extraction were included in the study. Remimazolam was administered as a single dose of 0.05 mg/kg followed by a continuous infusion at a rate of 0.35 mg/kg/h, with the infusion rate adjusted to maintain a sedation level at a Modified Observer's Assessment of Alertness/Sedation (MOAA/S) score of 2-4. The primary endpoint was the sedation success rate with remimazolam monotherapy, and the secondary endpoints included induction time, recovery time, time until discharge, remimazolam dose, respiratory and circulatory dynamics, and frequency of adverse events. RESULTS: The sedation success rate with remimazolam monotherapy was 100%. The remimazolam induction dose was 0.08 (0.07-0.09) mg/kg, and the anesthesia induction time was 3.2 (2.6-3.9) min. The mean infusion rate of remimazolam during the procedure was 0.40 (0.38-0.42) mg/kg/h. The time from the end of remimazolam administration to awakening was 8.0 (6.7-9.3) min, and the time from the end of remimazolam administration to discharge was 14.0 (12.5-15.5) min. There were no significant respiratory or circulatory effects requiring intervention during sedation. CONCLUSIONS: Continuous intravenous administration of remimazolam can achieve optimal sedation levels without significantly affecting respiratory or circulatory dynamics. The study also provided guidance on the appropriate dosage of remimazolam for achieving moderate sedation during dental procedures. Additionally, the study findings suggest that electroencephalogram monitoring can be a reliable indicator of the level of sedation during dental procedural sedation with remimazolam. TRIAL REGISTRATION: The study was registered in the Japan Registry of Clinical Trials (No. jRCTs061220052) on 30/08/2022.

Spinal Muscular Atrophy Type III Recognized After Delayed Recovery From Neuromuscular Blockade After an Orthognathic Surgery.

Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disease characterized by the degeneration of alpha motor neurons in the spinal cord, resulting in progressive proximal muscle weakness and paralysis. SMA is classified into types I-IV based on the age at symptom onset or maximum motor function achieved, and its clinical manifestations vary. SMA affects maxillofacial growth because of muscle dysfunction and results in abnormal maxillofacial morphology. In addition, definitive diagnosis is not often made because of the older onset age and symptoms are rarely severe. Therefore, the possibility of undiagnosed SMA in craniofacial surgeries must be considered. This report described a case of an SMA type III recognized after delayed recovery from the neuromuscular blockade in an orthognathic surgery under general anesthesia.

N-methyl-d-aspartate receptors and glycinergic transmission, respectively, mediate muscle relaxation and immobility of pentobarbital in mice.

Pentobarbital-induced anesthesia is believed to be mediated by enhancement of the inhibitory action of γ-aminobutyric acid (GABA)ergic neurons in the central nervous system. However, it is unclear whether all components of anesthesia induced by pentobarbital, such as muscle relaxation, unconsciousness, and immobility in response to noxious stimuli, are mediated only through GABAergic neurons. Thus, we examined whether the indirect GABA and glycine receptor agonists gabaculine and sarcosine, respectively, the neuronal nicotinic acetylcholine receptor antagonist mecamylamine, or the N-methyl-d-aspartate receptor channel blocker MK-801 could enhance pentobarbital-induced components of anesthesia. Muscle relaxation, unconsciousness, and immobility were evaluated by grip strength, the righting reflex, and loss of movement in response to nociceptive tail clamping, respectively, in mice. Pentobarbital reduced grip strength, impaired the righting reflex, and induced immobility in a dose-dependent manner. The change in each behavior induced by pentobarbital was roughly consistent with that in electroencephalographic power. A low dose of gabaculine, which significantly increased endogenous GABA levels in the central nervous system but had no effect on behaviors alone, potentiated muscle relaxation, unconsciousness, and immobility induced by low pentobarbital doses. A low dose of MK-801 augmented only the masked muscle-relaxing effects of pentobarbital among these components. Sarcosine enhanced only pentobarbital-induced immobility. Conversely, mecamylamine had no effect on any behavior. These findings suggest that each component of anesthesia induced by pentobarbital is mediated through GABAergic neurons and that pentobarbital-induced muscle relaxation and immobility may partially be associated with N-methyl-d-aspartate receptor antagonism and glycinergic neuron activation, respectively.

Analgesia-based Sedation for Oral Surgery in Patients With Chronic Respiratory Obstructive Disease.

Chronic obstructive pulmonary disease (COPD) is a risk factor for postoperative cardiovascular and respiratory complications. Thus, intravenous sedation can be a better option than general anesthesia for surgery in patients with severe COPD. Herein, we present 2 cases of analgesia-based sedation in patients with severe COPD who underwent oral surgery. The current study aimed to discuss these cases to provide knowledge about the appropriate sedation management in patients with this disease. In the current cases, the patients received sufficient analgesia and minimum sedation (analgesia-based sedation). Moreover, dexmedetomidine was used for maintaining sedation and fentanyl for analgesic effects. Furthermore, we focused on providing the maximum analgesic effect of local anesthesia. The patients' vital signs were stable. They did not have any psychological or physical complaints, such as anxiety and pain, during the procedure. Then, they were discharged from the hospital without any complications. Thus, analgesia-based sedation can be an alternative option for oral surgery in patients with COPD.

Difficult intubation and postoperative aspiration pneumonia associated with Moebius syndrome: a case report.

BACKGROUND: Moebius syndrome is a rare congenital disorder characterized by non-progressive palsy of the abducens (VI) and facial (VII) cranial nerves. Its common features include dysfunctions associated with other cranial nerves, orofacial abnormalities, skeletal muscle hypotonia, and other systemic disorders of differing severities. There are several concerns in the perioperative management of patients with Moebius syndrome. CASE PRESENTATION: We present a report on the management of general anesthesia of a 14-year-old male patient with Moebius syndrome who was scheduled for mandibular cystectomy. The patient was diagnosed with Moebius syndrome at the age of 7 years based on his clinical manifestations of nerve palsy since birth and cranial nerve palsy of the trigeminal (V), facial (VII), glossopharyngeal (IX), vagus (X), and sublingual nerves (XII). The patient's oral morphological abnormalities made intubation difficult. He also experienced dysphagia and aspiration pneumonia on a daily basis. Oral secretions were frequently suctioned postoperatively. However, after discharge, the patient developed aspiration pneumonia and was readmitted to the hospital. CONCLUSIONS: The main problem arising when administering general anesthesia to patients with this syndrome is difficult airway management. The oral abnormalities in these patients, such as small jaw and extreme dental stenosis, make mask ventilation and intubation difficult. Furthermore, this syndrome often involves respiratory impairment and dysphagia due to cerebral nerve palsy, so there is a high risk of postoperative respiratory complications. Since multiple organs are affected in patients with Moebius syndrome, appropriate perioperative management strategies must be prepared for these patients.

Pentobarbital may protect against neurogenic inflammation after surgery via inhibition of substance P release from peripheral nerves of rats.

The inflammatory response related to surgery is considered surgical inflammation. Most anesthetic agents directly or indirectly suppress the immune response. However, the intravenous anesthetics pentobarbital and ketamine were reported to inhibit the lipopolysaccharide-induced inflammatory response such as cytokines formation. Neurogenic inflammation is inflammation originating from the local release of inflammatory mediators, such as substance P (SP), by primary afferent neurons after noxious stimuli like surgery. Thus, in this study, we examined whether pentobarbital and ketamine suppress SP release from cultured dorsal root ganglion (DRG) neurons. DRG cells were dissected from male Wistar rats. Released SP was measured by radioimmunoassay. We demonstrated that higher concentrations of pentobarbital (100-1,000 µM) significantly inhibited capsaicin (100 nM)-induced, but not high K+ (50 mM)-induced, SP release from DRG cells, although a high concentration of ketamine (1 mM) did not. This study revealed that pentobarbital functions between the activation of vanilloid receptor subtype 1 (TRPV1) receptors, to which capsaicin selectively binds, and the opening of voltage-operated Ca2+ channels (VOCC) in the nerve endings. Therefore, the anti-inflammatory action of pentobarbital is mediated through different mechanisms than those of ketamine. Thus, the inhibitory effect of pentobarbital on SP release from peripheral terminals may protect against neurogenic inflammation after surgery.

Genomic insights into phage-host interaction in the deep-sea chemolithoautotrophic Campylobacterota, Nitratiruptor.

The genus Nitratiruptor represents one of the most numerically abundant chemolithoautotrophic Campylobacterota populations in the mixing zones of habitats between hydrothermal fluids and ambient seawater in deep-sea hydrothermal environments. We isolated and characterized four novel temperate phages (NrS-2, NrS-3, NrS-4, and NrS-5) having a siphoviral morphology, infecting Nitratiruptor strains from the Hatoma Knoll hydrothermal field in the southern-Okinawa Trough, Japan, and conducted comparative genomic analyses among Nitratiruptor strains and their phages. The Nitratiruptor temperate phages shared many potential core genes (e.g., integrase, Cro, two structural proteins, lysozyme, and MazG) with each other despite their diverse morphological and genetic features. Some homologs of coding sequences (CDSs) of the temperate phages were dispersed throughout the non-prophage regions of the Nitratiruptor genomes. In addition, several regions of the phage genome sequences matched to spacer sequences within clustered regularly interspaced short palindromic repeats (CRISPR) in Nitratiruptor genomes. Moreover, a restriction-modification system found in a temperate phage affected an epigenetic feature of its host. These results strongly suggested a coevolution of temperate phages and their host genomes via the acquisition of temperate phages, the CRISPR systems, the nucleotide substitution, and the epigenetic regulation during multiple phage infections in the deep-sea environments.

Efficacy of Chest Compressions Performed on Patients in Dental Chairs Versus on the Floor.

This study aimed to investigate the characteristics of chest compressions performed in dental chairs (DCs) with 2 different structural support designs and on the floor. This randomized prospective study was conducted to compare the effectiveness of chest compressions (rate and depth) using a feedback device and a manikin reporting system. The mean anterior chest wall motion measurements captured using the feedback device were significantly increased in the DCs than on the floor, whereas the percentage of net chest compression depths ≥5 cm as measured using the manikin reporting system were significantly decreased in the DCs than on the floor. These findings suggest that cardiopulmonary resuscitation performed in a DC without the use of a supporting stool or stiff backboard is not likely to be effective even if a DC design that incorporates a supportive steel column is utilized.

Usefulness of Tranexamic Acid Administration During Sagittal Split Ramus Osteotomy.

ABSTRACT: Tranexamic acid has been used to reduce intraoperative bleeding; however, its effect on anti-inflammation and the amount of drainage after orthognathic surgery is yet to be determined. Therefore, we aimed to examine the effect of tranexamic acid on intraoperative bleeding volume and operation time, amount of drainage, and anti-inflammation after orthognathic surgery. Forty healthy women who underwent bilateral sagittal split ramus osteotomy under general anesthesia participated in this study. The amount of intraoperative bleeding, the operation time, the amount of drainage, and the C-reactive protein level were compared between patients intravenously administered with tranexamic acid before surgery (before-surgery group) and those administered with the drug after surgery (after-surgery group). All data were analyzed using the Student t-test. Results were considered to be statistically significant when P < 0.05. Although no significant difference was found in the amount of drainage between the groups (P > 0.05), significant variations were detected in the amount of bleeding during surgery (before-surgery group: 161.7 ±â€Š45.3 mL versus after-surgery group: 270.2 ±â€Š24.0 mL; P = 0.0009), operation time (before-surgery group: 141.3 ±â€Š16.8 min versus after-surgery group: 166.8 ±â€Š24.9 min; P = 0.03), and postoperative C-reactive protein level (before-surgery group: 3.77 ±â€Š0.40 mg/dL versus after-surgery group: 5.02 ±â€Š0.75 mg/dL; P = 0.012) between the groups. In conclusion, administering tranexamic acid before surgery was found to significantly decrease bleeding, reduce operation time, and suppress postoperative inflammation.

The indirect γ-aminobutyric acid (GABA) receptor agonist gabaculine-induced loss of the righting reflex may inhibit the descending analgesic pathway.

In the spinal cord, γ-aminobutyric acid (GABA) interneurons play an essential role in antinociception. However, not all actions of GABA favor antinociception at the supraspinal level. We previously reported that gabaculine, which increases endogenous GABA in the synaptic clefts, induces loss of the righting reflex (LORR) that is one indicator of hypnosis, but not immobility in response to noxious stimulus. A slow pain is transmitted to the spinal cord via C fibers and evokes substance P (SP) release from their terminals. However, the antinociceptive effects of gabaculine are still unknown. Our study examined whether the analgesic effects of the opioid morphine or the α2-adrenoceptor agonist dexmedetomidine, whose actions are mediated through facilitation of the descending analgesic pathway, are affected by gabaculine-induced LORR. We also explored the effects of GABA receptor agonists on SP release from cultured dorsal root ganglion (DRG) neurons. All drugs were administered systemically to mice. To assess antinociception, loss of nociceptive response (analgesia) and immobility were evaluated. DRG cells were dissected from rats. Gabaculine produced no analgesia. Either morphine or dexmedetomidine in combination with gabaculine induced immobility; however, the doses of each drug required to induce immobility were much higher than those required to induce analgesia. Capsaicin significantly increased SP release from DRG cells, but a high concentration (1 mM) of the GABA receptor agonist muscimol, propofol, gaboxadol, or baclofen did not inhibit the capsaicin-induced SP release, suggesting that their antinociceptive effects were not through this mechanism. Thus, the gabaculine-induced LORR may inhibit the descending analgesic pathway.

NMDA and purinergic processes modulate neck muscle activity evoked by noxious stimulation of dura.

BACKGROUND: Adenosine triphosphate (ATP) and glutamate are associated with some headache conditions, and purinergic (P2X) and glutamatergic N-methyl-D-aspartate (NMDA) receptor-related processes in the medulla can modulate the effects of trigeminal nociceptive afferent inputs into the brainstem on craniofacial sensorimotor circuits. This study aimed to test whether neck muscle activity can be induced in rats by noxious stimulation of the frontal dura or superior sagittal sinus that involves P2X or NMDA receptor-dependent mechanisms. METHODS: While electromyographic activities of neck and craniofacial muscles were being recorded in anesthetized rats (n = 46), the inflammatory irritant mustard oil (0.2 µL, 20% MO) or vehicle (mineral oil) was topically applied to the dura or sinus, preceded by 10 µL of the ATP antagonist 2',3'-O-(2,4,6- trinitrophenyl) adenosine 5'-triphosphate (TNP-ATP, 0.1 mmol/L; n = 8) or 2-amino-5-phosphonopentanoic acid (APV, 0.05 mmol/L; n = 7) or phosphate-buffered saline (PBS as vehicle control; n = 10). RESULTS: Application of MO but not vehicle to the frontal dura significantly increased (P < .05) neck electromyographic activity whereas MO application to the superior sagittal sinus did not significantly increase neck electromyographic activity unless MO had previously been applied to the dura. Pre-treatment (i.t.) with TNP-ATP or APV but not vehicle control significantly reduced neck electromyographic activity evoked by MO application to the dura. CONCLUSIONS: These data suggest that noxious stimulation of the frontal dura (but not superior sagittal sinus) may enhance neck muscle activity that is P2X and NMDA receptor-dependent. These effects may contribute to neck muscle stiffness that occurs in some headache conditions.

Effective Postoperative Analgesia Using Intravenous Flurbiprofen and Acetaminophen.

PURPOSE: Management of postoperative pain is one of the most important components in postoperative care, because most patients have pain after dental surgery. The aim of this study was to evaluate whether acetaminophen could be an alternative to fentanyl in combination with a nonsteroidal anti-inflammatory drug (NSAID) as an analgesic after dental surgery in cases in which narcotic drugs were contraindicated. MATERIALS AND METHODS: Patients were 24- to 54-year-old men who underwent enucleation of a mandibular cyst under general anesthesia. The authors measured time from discontinuation of anesthetic administration until discharge from the operating room and postoperative pain during 4 hours after discharge. They compared these parameters between patients who were intravenously administered an NSAID such as flurbiprofen with fentanyl (NSAID/fentanyl group) and those administered an NSAID with acetaminophen (NSAID/acetaminophen group). Parametric data of time were analyzed using Student t test. Nonparametric data of the analgesic effect were analyzed using Mann-Whitney U test. RESULTS: Time until discharge from the operating room after discontinuation of anesthetics in the NSAID/fentanyl group was significantly longer than that in the NSAID/acetaminophen group (P < .05). In contrast, there was no significant difference in analgesic effect between the NSAID/acetaminophen and NSAID/fentanyl groups (P > .05). CONCLUSION: Although recovery time in the operating room of the flurbiprofen and acetaminophen group was markedly shorter than that of the flurbiprofen and fentanyl group, the postoperative analgesic effects of the 2 drugs were equipotent. Therefore, acetaminophen can be an alternative to fentanyl in cases in which narcotic drugs are contraindicated.

Quantitative Viral Community DNA Analysis Reveals the Dominance of Single-Stranded DNA Viruses in Offshore Upper Bathyal Sediment from Tohoku, Japan.

Previous studies on marine environmental virology have primarily focused on double-stranded DNA (dsDNA) viruses; however, it has recently been suggested that single-stranded DNA (ssDNA) viruses are more abundant in marine ecosystems. In this study, we performed a quantitative viral community DNA analysis to estimate the relative abundance and composition of both ssDNA and dsDNA viruses in offshore upper bathyal sediment from Tohoku, Japan (water depth = 500 m). The estimated dsDNA viral abundance ranged from 3 × 106 to 5 × 106 genome copies per cm3 sediment, showing values similar to the range of fluorescence-based direct virus counts. In contrast, the estimated ssDNA viral abundance ranged from 1 × 108 to 3 × 109 genome copies per cm3 sediment, thus providing an estimation that the ssDNA viral populations represent 96.3-99.8% of the benthic total DNA viral assemblages. In the ssDNA viral metagenome, most of the identified viral sequences were associated with ssDNA viral families such as Circoviridae and Microviridae. The principle components analysis of the ssDNA viral sequence components from the sedimentary ssDNA viral metagenomic libraries found that the different depth viral communities at the study site all exhibited similar profiles compared with deep-sea sediment ones at other reference sites. Our results suggested that deep-sea benthic ssDNA viruses have been significantly underestimated by conventional direct virus counts and that their contributions to deep-sea benthic microbial mortality and geochemical cycles should be further addressed by such a new quantitative approach.

Assessment of safety and efficacy of lamotrigine over the course of 1-year observation in Japanese patients with bipolar disorder: post-marketing surveillance study report.

BACKGROUND: A post-marketing surveillance (PMS) study was conducted with a 1-year observation period to assess the safety and efficacy of lamotrigine in routine clinical practice in patients with bipolar disorder (BD). PATIENTS AND METHODS: Central enrollment method was used to recruit patients diagnosed with BD who were being treated for the first time with lamotrigine to prevent the recurrence/relapse of BD mood episodes. Adverse drug reactions (ADRs) and recurrence/relapse were assessed. Improvement of mania and depression was also assessed using the Hamilton's Rating Scale for Depression (HAM-D) and the Young Mania Rating Scale (YMRS) at treatment initiation, 4-6 months post treatment initiation, and 10-12 months post treatment initiation. RESULTS: A total of 237/989 patients (24.0%) reported ADRs, most commonly rash (9.1%), and the incidence of serious ADRs was 3.3% (33/989 patients). Skin disorders occurred in 130 patients (13.1%), mostly within 8 weeks post treatment. A total of 237/703 patients (33.7%) experienced recurrence/relapse of mood episodes. The 25th percentile of the time to recurrence/relapse of mood episodes was 105 days. Remission of depression symptoms (HAM-D ≤7) occurred in 147/697 patients (21.1%) at treatment initiation, rising to 361 patients (67.4%) at 10-12 months post treatment. Remission of manic symptoms (YMRS ≤13) occurred in 615/676 patients (91.0%) at treatment initiation, rising to 500 patients (97.3%) at 10-12 months post treatment. CONCLUSION: The results of this PMS study suggest that lamotrigine is a well-tolerated and effective drug for preventing recurrence/relapse of BD in clinical practice.

Anesthetic Management of a Patient With Takayasu Arteritis.

Takayasu arteritis is a rare chronic progressive panendarteritis involving the aorta and its main branches. Anesthesia in patients with this disease can be complicated by severe uncontrolled hypertension, end-organ dysfunction, and stenosis of major blood vessels. In this case, general anesthesia was induced with sevoflurane and remifentanil without complications. To prevent intraoperative complications, we conducted intubation with a rigid video laryngoscope with careful consideration of the concentrations of analgesics and sedatives used. This case demonstrates the importance of anesthetic techniques for maintaining adequate tissue perfusion without hemodynamic changes in the anesthetic management of patients with Takayasu arteritis.

Lymphangioleiomyomatosis and multifocal micronodular pneumocyte hyperplasia in Japanese patients with tuberous sclerosis complex.

BACKGROUND: Pulmonary involvement in tuberous sclerosis complex (TSC) includes lymphangioleiomyomatosis (LAM) and multifocal micronodular pneumocyte hyperplasia (MMPH). This retrospective study investigated pulmonary involvement in Japanese TSC patients and pulmonary function testing in TSC-LAM. METHODS: The study subjects included 59 TSC patients (age range: 13-66, 15 males and 44 females). Female patients were divided into 3 groups (Group 1: symptomatic LAM, Group 2: asymptomatic LAM, Group 3: without LAM) and 3 cystic grades according to increasing cyst numbers on computed tomography images (patients without LAM, Grade 1 patients, and Grade 2+Grade 3 patients). The results of pulmonary function tests were compared among the groups and the grades. RESULTS: One male (6.7%) patient and 19 female (43.2%) patients were diagnosed with LAM and 7 male (43.2%) and 23 female (52.3%) patients were diagnosed with MMPH. Patients with multiple pulmonary nodules had higher rates of renal angiomyolipoma and history of seizures than patients without nodules. Although all 6 adolescent patients displayed no pulmonary symptoms, MMPH was found in 3 patients and LAM was found in a 13-year-old girl. Carbon monoxide diffusing capacity (DLco) differed significantly among the 3 groups and DLco and carbon monoxide diffusing capacity divided by the alveolar volume (DLco/VA) differed significantly among the 3 cystic grades. CONCLUSIONS: There was no difference in the prevalence of pulmonary involvement in TSC patients among countries. LAM and MMPH occur even during adolescence in TSC patients. DLco and the number of cysts are useful predictors of onset and progression of TSC-LAM.