Nuclear Imaging Data-Driven Classification of Parkinson's Disease.

BACKGROUND: Parkinson's disease (PD) is a heterogeneous neurodegenerative disorder characterized by motor and nonmotor symptoms. Several features have prognostic importance and have been used as key indicators for identifying clinical subtypes. However, the symptom-based classification approach has limitations with respect to the stability of the obtained subtypes. OBJECTIVES: The purpose of this study was to identify subtypes of PD using nuclear imaging biomarkers targeting the cardiac sympathetic nervous and nigro-striatal systems and to compare patterns of cortical morphological change among obtained subtypes. METHODS: We performed unbiased hierarchical cluster analysis using 123 I-metaiodobenzylguanidine cardiac scintigraphy and 123 I-N-(3-fluoropropyl)-2ß-carbomethoxy-3ß-(4-iodophenyl) nortropane single photon emission computed tomography data for 56 patients with PD. We compared clinical characteristics and the patterns of cortical atrophy in the obtained clusters. RESULTS: Three clusters were identified and showed distinct characteristics in onset ages and dopamine-replacement therapy and deep brain stimulation requirements. According to the characteristics, clusters were classified into two subtypes, namely, "cardio-cortical impairment (CC)" and "dopaminergic-dominant dysfunction (DD)" subtype. The three clusters were named according to subtype and time since onset in which 14 patients were classified as "early DD," 25 as "advanced DD," and 17 as "early CC." Compared with the early DD subtype, the early CC subtype showed parietal-dominant diffuse cortical atrophy and the advanced DD subtype showed left-side predominant mild cortical atrophy. CONCLUSIONS: Nuclear imaging biomarker-based classification can be used to identify clinically and pathologically relevant PD subtypes with distinct disease trajectories. © 2023 International Parkinson and Movement Disorder Society.

A patient with a 6q22.1 deletion and a phenotype of non-progressive early-onset generalized epilepsy with tremor.

We report a patient with a 6q22.1 deletion, who presented with a rare syndrome of generalized epilepsy, myoclonic tremor, and intellectual disability. There was no clinical progression after follow-up for more than 10 years. Our report presents the genetic basis for a phenotype involving a non-progressive generalized epilepsy with tremor. The efficacy of valproic acid for seizure control and the partial efficacy of deep brain stimulation with propranolol for myoclonic tremor is detailed.

Phase I trial of convection-enhanced delivery of nimustine hydrochloride (ACNU) for brainstem recurrent glioma.

BACKGROUND: Treatment options for patients suffering brainstem gliomas are quite limited as surgery is not an option against intrinsic tumors at brainstem and chemotherapy generally failed to demonstrate its efficacy. Intracerebral convection-enhanced delivery (CED) is a novel approach for administering chemotherapy to patients with brain tumors. We present the results of phase I trial of CED of nimustine hydrochloride (ACNU), designed to determine the maximum tolerable concentration of ACNU, for patients with recurrent brainstem gliomas. METHODS: Sixteen patients, aged 3-81 years old, suffering from recurrent brainstem gliomas, including diffuse intrinsic pontine glioma patients as well as patients with recurrent gliomas that originated from non-brainstem sites, were enrolled in this trial between February 2011 and April 2016. The dose/concentration escalation trial included 3 dose/concentration groups (0.25, 0.5, and 0.75 mg/mL, all at 7 mL) to determine the safety and tolerability of CED of ACNU. Real-time monitoring of drug distribution was performed by mixing gadolinium-tetraazacyclododecanetetraacetic acid (Gd-DOTA) in the infusion solution. CED of ACNU was given in combination with oral or intravenous temozolomide chemotherapy. RESULTS: CED of ACNU demonstrated antitumor activity, as assessed by radiographic changes and prolonged overall survival. The recommended dosage was 0.75 mg/mL. Drug-associated toxicity was minimal. CONCLUSIONS: Intracerebral CED of ACNU under real-time monitoring of drug distribution, in combination with systemic temozolomide, was well tolerated among patients with recurrent brainstem gliomas. The safety and efficacy observed suggest the clinical benefits of this strategy against this devastating disease. Based on this phase I study, further clinical development of ACNU is warranted.

An investigation into the effects and prognostic factors of cognitive decline following subthalamic nucleus stimulation in patients with Parkinson's disease.

We retrospectively investigated the effects of subthalamic nucleus stimulation (STN-DBS) on new postoperative onset of cognitive decline and prognostic factors for advanced Parkinson's disease (PD). We studied 39 PD patients who had received bilateral STN-DBS. Clinical symptoms, cognitive function, psychiatric function, and health-related quality of life (HRQOL) were assessed before and six months after surgery. Based on the results of neuropsychological examinations six months after the surgery, the subjects were divided into those with and those without cognitive decline. We compared pre- and post-operative assessments between the two groups. Prognostic factors were investigated using multiple logistic regression analyses. Seven patients had cognitive decline six months after the operation (17.9%); they were significantly older than those without cognitive decline. Preoperative neuropsychological examinations revealed impairments in language and executive function. No differences were found in clinical symptoms. Patients with cognitive decline had significantly worse apathy scale scores. The HRQOL revealed significant declines in the Mental Component Summary (MCS), vitality, and mental health (MH) domains. Postoperative comparisons revealed novel significant differences in activities of daily living in the "on" and "off" states and in daytime drowsiness. Preoperative differences seen in the MCS and vitality indices were no longer present. Word fluency, and apathy scale and MH scores were independent preoperative prognostic factors for cognitive decline. New postoperative onset of cognitive decline due to STN-DBS affected activities of daily living and psychiatric function. Preoperative non-motor symptoms may be prognostic factors for new onset of cognitive decline.

Summary of 15 years experience of awake surgeries for neuroepithelial tumors in tohoku university.

We retrospectively analyzed 15 years experience of awake surgeries for neuroepithelial tumors in Tohoku University. Awake surgeries mostly for language mapping were performed for 42 of 681 newly diagnosed cases (6.2%) and 59 of 985 surgeries including for recurrence (6.0%). When the same histologies and locations as cases resected under awake condition are selected from the parent population treated by radical resection, awake surgeries were most frequently performed for 14 of 55 newly diagnosed cases (25.5%) and 14 of 62 surgeries (22.6%) with grade II gliomas. In the results, 8 of 59 surgeries (13.6%) could not achieve complete language monitoring until the final stage of tumor resection, considered as failed awake surgery. Gross total resection was accomplished in 20 of 42 newly diagnosed cases (47.6%) and 32 of 59 surgeries (54.2%). Mortality rate was 0%. Late severe deficits were observed in 2 of 42 newly diagnosed cases (4.8%) and 3 of 59 surgeries (5.1%). Negative language mapping cases did not suffer severe deficits in both early and late stages. In contrast, high incidence of severe deficits, 3 as early and 2 as late of 8 cases, were identified with failed awake surgery. The overall survival of patients treated by awake surgery compared favorably with those treated without stimulation mapping and with stimulation mapping under general anesthesia. Awake surgery may contribute to improve the outcome of gliomas near eloquent areas by maximizing the tumor resection and minimizing the surgical morbidity.

Use of microscope-integrated near-infrared indocyanine green videoangiography in the surgical treatment of intramedullary cavernous malformations: report of 8 cases.

OBJECT: The characteristics and efficacy of indocyanine green (ICG) videoangiography in cavernous malformation (CM) have not been fully elucidated. The purpose of this paper is to examine the potential utility of ICG videoangiography in the surgical treatment of intramedullary CMs. METHODS: The authors conducted a retrospective review of 8 cases involving 5 men and 3 women who had undergone surgery for intramedullary CM between January 2008 and July 2011. All patients were evaluated by means of MRI. The MRI findings and clinical history in all cases suggested intramedullary CM as a preoperative diagnosis. In 2 of 8 cases, dilated venous structures associated with CMs were demonstrated. In one of these cases, there were coexisting extramedullary CMs. Intraoperatively, ICG fluorescence was observed for 5 minutes using microscope-integrated videoangiography. RESULTS: In all 8 cases, intra- and extramedullary CMs were seen as avascular areas on ICG videoangiography. Indocyanine green videoangiography helped surgeons to localize and predict margins of the lesions before performing myelotomy. Importantly, in the cases with associated venous anomalies, ICG videoangiography was useful in delineating and preserving the venous structures. In extramedullary CMs located dorsal to the spinal cord, gradual ICG infiltration was seen, starting at 110 seconds and maximal at 210 seconds after injection. Postoperative MRI confirmed total removal of the lesions in all cases, and subsequent recovery of all patients was uneventful. CONCLUSIONS: Indocyanine green videoangiography provided useful information with regard to the detection of lesion margins by demonstrating intramedullary CMs as avascular areas. In cases associated with venous anomalies, ICG contributed to safe and complete removal of the CMs by visualizing the venous structure. In extramedullary CMs, ICG videoangiography demonstrated the characteristic of slow blood flow within CMs.

5-aminolevulinic acid fluorescence-guided resection of intramedullary ependymoma: report of 9 cases.

BACKGROUND: Resection guided by 5-aminolevulinic acid (5-ALA) fluorescence has proved to be useful in intracranial glioma surgery. However, the effects of 5-ALA on spinal cord tumors remain unknown. OBJECTIVE: To evaluate the usefulness of 5-ALA fluorescence-guided resection of intramedullary ependymoma for achieving maximum tumor resection. METHODS: This study included 10 patients who underwent surgical resection of an intramedullary ependymoma. Nine patients were orally administered 5-ALA (20 mg/kg) 2 hours before the induction of anesthesia. 5-ALA fluorescence was visualized with an operating microscope. Tumors were removed in a standardized manner with electrophysiological monitoring. The extent of resection was evaluated on the basis of intraoperative findings and postoperative magnetic resonance imaging. Histopathological diagnosis was established according to World Health Organization 2007 criteria. Cell proliferation was assessed by Ki-67 labeling index. RESULTS: 5-ALA fluorescence was positive in 7 patients (6 grade II and 1 grade III) and negative in 2 patients (grade II). Intraoperative findings were dichotomized: Tumors covered by the cyst were easily separated from the normal parenchyma, whereas tumors without the cyst appeared to be continuous to the spinal cord. In these cases, 5-ALA fluorescence was especially valuable in delineating the ventral and cranial and caudal margins. Ki-67 labeling index was significantly higher in 5-ALA-positive cases compared with 5-ALA-negative cases. All patients improved neurologically or stabilized after surgery. CONCLUSION: 5-ALA fluorescence was useful for detecting tumor margins during surgery for intramedullary ependymoma. When combined with electrophysiological monitoring, fluorescence-guided resection could help to achieve maximum tumor resection safely.

Regression of recurrent glioblastoma infiltrating the brainstem after convection-enhanced delivery of nimustine hydrochloride.

This 13-year-old boy with a history of cranial irradiation for the CNS recurrence of acute lymphocytic leukemia developed a glioblastoma in the right cerebellum. Resection and chemo- and radiotherapy induced remission of the disease. However, recurrence was noted in the brainstem region 8 months later. Because no effective treatment was available for this recurrent lesion, the authors decided to use convection-enhanced delivery (CED) to infuse nimustine hydrochloride. On stereotactic insertion of the infusion cannula into the brainstem lesion, CED of nimustine hydrochloride was performed with real-time MR imaging to monitor the co-infused chelated gadolinium. The patient's preinfusion symptom of diplopia disappeared after treatment. Follow-up MR imaging revealed the response of the tumor. The authors report on a case of recurrent glioblastoma infiltrating the brainstem that regressed after CED of nimustine hydrochloride.

Differentiation of clear cell ependymoma of the cerebellum from hemangioblastoma by thallium-201 single photon emission computed tomography-case report-.

A 57-year-old man suffered from dizziness for about one year and truncal ataxia for about one month. Magnetic resonance imaging demonstrated a cystic tumor with a homogeneously enhanced mural nodule located in the cerebellar vermis. Computed tomography angiography revealed a hypervascular nodule. These findings were compatible with hemangioblastoma. Thallium-201 single photon emission computed tomography ((201)Tl-SPECT) showed moderately high uptake in the early phase and moderately high retention in the delayed phase, whereas hemangioblastoma shows almost no retention in the delayed phase. The patient underwent total removal of the tumor. The histological diagnosis was clear cell ependymoma (CCE). CCE is a rare subtype of ependymoma, which resembles hemangioblastoma in histological and neuroimaging findings, but is considerably more aggressive. (201)Tl-SPECT can provide useful information for the preoperative differential diagnosis of infratentorial CCE and hemangioblastoma.

[Intraoperative neuronavigation system without rigid pin fixation].

OBJECT: Integration of neuronavigation into brain tumor surgery can improve the accuracy and precision of resection, but most neuronavigation systems require rigid pin fixation of the patient's head throughout the operation. We describe use of a noninvasive skull reference tool, which can replace rigid pin fixation in awake craniotomy and pediatric surgery, when standard pin fixation cannot be used. METHODS AND RESULTS: The skull reference tool (BrainLAB, Munich, Germany) is directly attached to the outer skull with a small self-tapping screw. Virtual scanning of the surface of the face and head achieves patient registration in seconds without requiring the use of fiducial markers or head fixation. This procedure improves patient comfort, cooperativeness, and compliance, resulting in better operating procedures. This skull reference tool is available for children younger than 3 years of age, in whom pin fixing is dangerous. Twelve patients underwent awake surgery and four pediatric patients younger than 3 years old underwent five procedures using this skull reference tool in our hospital between January 2005 and December 2008. The method of utilizing this skull reference tool was easy and sufficiently accurate in these patients. CONCLUSION: The use of this skull reference tool provides an accurate and comfortable method of frameless navigation in patients undergoing awake craniotomy and pediatric patients.

Neuroendoscopic management of symptomatic septum pellucidum cavum vergae cyst using a high-definition flexible endoscopic system.

A 24-year-old man, who had an asymptomatic septum pellucidum cyst incidentally found one year previously, presented with severe headache and right abducens nerve palsy caused by expansion of the midline cyst. Preoperative magnetic resonance (MR) imaging revealed obstructive hydrocephalus due to the enlarged midline cyst. Neuroendoscopic fenestration of the septum pellucidum cyst was successfully performed via a right frontal approach using a high-resolution flexible neuroendoscopic system without complication. Communication between the cyst cavity and bilateral lateral ventricles was constructed via a single trajectory. The entire inner cyst wall could be inspected from the cyst cavity by manipulating the flexible neuroendoscopic system, which excluded the presence of neoplasm. His symptoms were completely relieved after surgery, and postoperative MR imaging showed significant improvement of hydrocephalus and shrinkage of the midline cyst. Septum pellucidum cavum vergae cyst may expand and become symptomatic, so fenestration using a flexible neuroendoscope system may be the optimal method for constructing communication to the bilateral lateral ventricles with minimal invasion.

[Neuroendoscopic management of a colloid cyst at the third ventricle using the high-definition flexible neuroendoscopic system: report of two cases].

Colloid cysts are benign intracranial lesions located at the anterior roof of the third ventricle, which can result in the obstruction of the foramen of Monro and subsequent hydrocephalus or sudden death. Colloid cysts have been treated by microsurgical resection or by stereotactic aspiration. More recently, the use of rigid neuroendoscopy for colloid cysts has been attempted, but the efficacy of the flexible neuroendoscopic system is undetermined except for limited reports. A 40-year-old man and a 52-year-old man were presented with obstructive hydrocephalus owing to colloid cysts in the third ventricle, who were diagnosed by the typical findings of pre-operative CT scan and MRI. In the first case, endoscopic resection of the cyst was attempted using a high-definition flexible neuroendoscopic system with a CCD camera at the tip of the endoscope. The procedure relieved his symptoms. Hydrocephalus was improved after surgery, and postoperative MRI revealed the disappearance of the third ventricle lesion. Histological examination confirmed the diagnosis of colloid cyst. In the second case, endoscopic removal of the cyst wall and the evacuation of the cyst content were attempted using a high-definition flexible endoscopic system which resulted in the improvement of hydrocephalus and marked shrinkage of the third ventricle lesion observed in postoperative MRI. There was no recurrence in either patient. We recommend endoscopic treatment for colloid cysts using the high-definition neuroendoscopic system, which enables safe and thorough manipulation of the lesion and surrounding structures.

[Clinical features and significance of negative motor response in intraoperative language mapping during awake craniotomy].

The negative motor area and anterior and posterior language areas were localized by intraoperative electrical cortical stimulation under the awake condition to evaluate the clinical significance of these areas. Thirty-seven awake craniotomies with language mapping were performed in 36 patients with brain tumors. The negative motor area was determined in 17 cases, and the anterior and posterior language areas were found in 12 and 6 cases, respectively. The negative motor area was located in the precentral gyrus inferior to the orofacial motor area in 16 cases, and in the inferior frontal gyrus anterior to the orofacial motor area in one case. Both the negative motor area and the anterior language area were determined in 8 cases. Anterior language areas in these 8 cases were located anterior and/or inferior to the negative motor areas. The negative motor area is an easily determined, important landmark for intraoperative language mapping.

Surgical implications of neuromagnetic spike localization in temporal lobe epilepsy.

PURPOSE: To investigate the clinical usefulness of magnetoencephalography (MEG) as a guide to the surgical treatment of temporal lobe epilepsy (TLE). METHODS: Preoperative spike localization by MEG was compared with seizure outcome and postoperative spike localization at 12 months after resective surgery in 16 patients with TLE. Spike localization was classified into anterior temporal (AT) and non-AT localization in 11 patients without neocortical lesion treated with anterior temporal lobectomy (ATL); and lesion and lobar localization in five patients with neocortical lesion treated with lesionectomy (n = 3) or lesionectomy with medial temporal resection (n = 2). RESULTS: All five patients with AT localization became seizure free and spike free after surgery. Among the six patients with non-AT localization, two became seizure free and spike free, two became seizure free with residual spikes, one had residual seizures but no spikes, and one had both residual seizures and spikes. All three patients with lesion localization and two with lobar localization had favorable seizure outcome and became spike free after surgery. CONCLUSIONS: MEG spike localization can identify neocortical sources remote from the presumed epileptogenic area. Favorable seizure outcome can be expected in patients with AT localization after ATL and patients with lesion localization after lesionectomy. In contrast, non-AT localization indicates either nonmedial TLE or spike propagation to the posterior and extratemporal neocortex. Similarly, lobar localization indicates spike propagation from an epileptogenic lesion or extensive epileptogenicity. Patients with non-AT localization or lobar localization should undergo intensive evaluations, such as intracranial EEG, for improved seizure outcome.