Non-motor symptoms can severely affect the quality of life of Parkinson's disease-afflicted patients, with the most common ones being pain, sleep impairments, and neuropsychiatric manifestations. In advanced cases, complex fluctuations of motor and non-motor symptoms can occur despite optimal medication. Research on deep brain stimulation of the subthalamic nucleus suggests that it may provide benefits for treating non-motor symptoms in addition to improving motor symptoms. With recent advancements in deep brain stimulation technology, simultaneous recording of local field potentials and delivery of therapeutic stimulation is possible. This opens new possibilities for better understanding the pathophysiology of non-motor symptoms in Parkinson's disease and for identifying potential electrophysiological biomarkers that accurately represent these symptoms. Specifically, this review aims to highlight potential local field potential biomarkers of non-motor symptoms in the subthalamic nucleus. The main findings indicate that activities in the beta frequency band are associated with nociception and sleep impairments such as insomnia and rapid eye movement sleep behavior disorders. Additionally, activities in the theta and alpha frequency bands seem to reflect neurocognitive manifestations, including depression and impulse control disorders. A better understanding of these biomarkers could improve the clinical management of non-motor symptoms in Parkinson's disease. They hold promise for adjusting deep brain stimulation parameters in open-loop settings and might eventually be applied in closed-loop deep brain stimulation systems, though their true impact remains uncertain.

Background and purpose: To evaluate the reliability and accuracy of nonaneurysmal perimesencephalic subarachnoid hemorrhage (NAPSAH) on Noncontrast Head CT (NCCT) between numerous raters. Materials and methods: 45 NCCT of adult patients with SAH who also had a catheter angiography (CA) were independently evaluated by 48 diverse raters; 45 raters performed a second assessment one month later. For each case, raters were asked: 1) whether they judged the bleeding pattern to be perimesencephalic; 2) whether there was blood anterior to brainstem; 3) complete filling of the anterior interhemispheric fissure (AIF); 4) extension to the lateral part of the sylvian fissure (LSF); 5) frank intraventricular hemorrhage; 6) whether in the hypothetical presence of a negative CT angiogram they would still recommend CA. An automatic NAPSAH diagnosis was also generated by combining responses to questions 2 -5. Reliability was estimated using Gwet 's AC1 ( K G ), and the relationship between the NCCT diagnosis of NAPSAH and the recommendation to perform CA using Cramer 's V test. Multi -rater accuracy of NCCT in predicting negative CA was explored. Results: Inter -rater reliability for the presence of NAPSAH was moderate ( K G = 0.58; 95%CI: 0.47, 0.69), but improved to substantial when automatically generated ( K G = 0.70; 95%CI: 0.59, 0.81). The most reliable criteria were the absence of AIF filling ( K G = 0.79) and extension to LSF ( K G = 0.79). Mean intra-rater reliability was substantial ( K G = 0.65). NAPSAH weakly correlated with CA decision ( V = 0.50). Mean sensitivity and specificity were 58% (95%CI: 44%, 71%) and 83 % (95%CI: 72 %, 94%), respectively. Conclusion: NAPSAH remains a diagnosis of exclusion. The NCCT diagnosis was moderately reliable and its impact on clinical decisions modest. (c) 2024 The Authors. Published by Elsevier Masson SAS. This is an open access article under the CC BY -NC -ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

ABSTRACT:Objective:Intracerebral abscess is a life-threatening condition for which there are no current, widely accepted neurosurgical management guidelines. The purpose of this study was to investigate Canadian practice patterns for the medical and surgical management of primary, recurrent, and multiple intracerebral abscesses.Methods:A self-administered, cross-sectional, electronic survey was distributed to active staff and resident members of the Canadian Neurosurgical Society and Canadian Neurosurgery Research Collaborative. Responses between subgroups were analyzed using the Chi-square test.Results:In total, 101 respondents (57.7%) completed the survey. The majority (60.0%) were staff neurosurgeons working in an academic, adult care setting (80%). We identified a consensus that abscesses >2.5 cm in diameter should be considered for surgical intervention. The majority of respondents were in favor of excising an intracerebral abscess over performing aspiration if located superficially in non-eloquent cortex (60.4%), located in the posterior fossa (65.4%), or causing mass effect leading to herniation (75.3%). The majority of respondents were in favor of reoperation for recurrent abscesses if measuring greater than 2.5 cm, associated with progressive neurological deterioration, the index operation was an aspiration and did not include resection of the abscess capsule, and if the recurrence occurred despite prior surgery combined with maximal antibiotic therapy. There was no consensus on the use of topical intraoperative antibiotics.Conclusion:This survey demonstrated heterogeneity in the medical and surgical management of primary, recurrent, and multiple brain abscesses among Canadian neurosurgery attending staff and residents.1

Background: Following craniotomy, there is widespread agreement that post-operative neurological impairments require specialized evaluation to evaluate fitness to drive. However, for patients who had a craniotomy and do not have neurological deficits or known seizures, there is less consensus as to when return to driving is safe. In this study, we aim to review existing guidelines regarding driving post-craniotomy and assess the current practices for post-craniotomy recommendations in Canada. Methods: Our study has three components: 1) systematic review of existing guidelines for return to driving after cranial procedure; 2) review of primary evidence (cohort studies) regarding seizure risk following a craniotomy, depending of the underlying pathology; 3) online questionnaire distributed to Canadian neurosurgeons by the Canadian Neurosurgery Collaborative (CNRC) network. Results: Our systematic review unveiled various sets of guidelines for driving after a craniotomy. For instance, UK Driving and Vehicle Licensing Agency writes into law specific guidelines for return to driving varying based on underlying pathology. Their results were drawn from large cohort studies measuring the occurrence of post-operative seizures after craniotomy for a variety of conditions. The questionnaire is currently being distributed to Canadian neurosurgeons. Conclusions: Our study lays the first steps towards the development of Canadian guidelines for return to driving post-craniotomy.

Invasive brain-computer interfaces hold promise to alleviate disabilities in individuals with neurologic injury, with fully implantable brain-computer interface systems expected to reach the clinic in the upcoming decade. Children with severe neurologic disabilities, like quadriplegic cerebral palsy or cervical spine trauma, could benefit from this technology. However, they have been excluded from clinical trials of intracortical brain-computer interface to date. In this manuscript, we discuss the ethical considerations related to the use of invasive brain-computer interface in children with severe neurologic disabilities. We first review the technical hardware and software considerations for the application of intracortical brain-computer interface in children. We then discuss ethical issues related to motor brain-computer interface use in pediatric neurosurgery. Finally, based on the input of a multidisciplinary panel of experts in fields related to brain-computer interface (functional and restorative neurosurgery, pediatric neurosurgery, mathematics and artificial intelligence research, neuroengineering, pediatric ethics, and pragmatic ethics), we then formulate initial recommendations regarding the clinical use of invasive brain-computer interfaces in children.

ABSTRACT: Background: Non-penetrating head and neck trauma is associated with extracranial traumatic vertebral artery injury (eTVAI) in approximately 1–2% of cases. Most patients are initially asymptomatic but have an increased risk for delayed stroke and mortality. Limited evidence is available to guide the management of asymptomatic eTVAI. As such, we sought to investigate national practice patterns regarding screening, treatment, and follow-up domains. Methods: A cross-sectional, electronic survey was distributed to members of the Canadian Neurosurgical Society and Canadian Spine Society. We presented two cases of asymptomatic eTVAI, stratified by injury mechanism, fracture type, and angiographic findings. Screening questions were answered prior to presentation of angiographic findings. Survey responses were analyzed using descriptive statistics. Results: One hundred-eight of 232 (46%) participants, representing 20 academic institutions, completed the survey. Case 1: 78% of respondents would screen for eTVAI with computed topography angiography (CTA) (97%), immediately (88%). The majority of respondents (97%) would treat with aspirin (89%) for 3–6 months (46%). Respondents would follow up clinically (89%) or radiographically (75%), every 1–3 months. Case 2: 73% of respondents would screen with CTA (96%), immediately (88%). Most respondents (94%) would treat with aspirin (50%) for 3–6 months (35%). Thirty-six percent of respondents would utilize endovascular therapy. Respondents would follow up clinically (97%) or radiographically (89%), every 1–3 months. Conclusion: This survey of Canadian practice patterns highlights consistency in the approach to screening, treatment, and follow-up of asymptomatic eTVAI. These findings are relevant to neurosurgeons, spinal surgeons, stroke neurologists, and neuro-interventionalists.

-BACKGROUND: Aneurysms of spinal arteries not associated with any known predisposing condition are referred to as isolated spinal aneurysms (SAs). In our series, an SA was found in 2 patients during the postpartum period. The goal of this study is to determine whether an occurrence of an SA may be related to puerperium. -METHODS: In a retrospective analysis of our consecutive series of 10 cases of SAs from 2008 to 2020, we identified 2 cases of SAs during puerperium. Patients' charts and imaging were reviewed, for potential predisposing factors. -RESULTS: In both cases, angiography showed fusiform aneurysms of the anterior SA with concomitant bilateral vertebral artery (VA) dissections. Serum vasculitis and inflammatory panel and genetic testing for collagen disorders were negative in both cases. Review of the literature showed that pregnancy is associated with an increased risk of arterial dissections in various locations and supports the hypothesis that hemodynamic and hormonal changes may play a role in the formation of SAs. -CONCLUSIONS: Pregnancy and peripartum state may be a distinct cause of the formation of SAs, possibly as a result of increased hemodynamic stress and hormonal changes that may alter the arterial wall. It would be appropriate to add pregnancy as a subgroup in the classification of SAs. In our series, both cases were associated with bilateral VA dissections; it is possible that the bilateral VA stenosis may have contributed to the formation of the SAs. It is important to recognize this possibility when considering the occlusion of a dissected VA.

As 70% of spinal cord injuries (SCI) are anatomically incomplete, partial motor recovery may occur. Unfortunately, recovery is rarely satisfactory and multiple life-long deficits persist. We developed a neuroprosthesis whereby electrical microstimulation was delivered to the motor cortex during ongoing locomotion to improve the execution and training of voluntary movements. When the animal attempts to perform a movement, the electrode micro-stimulates the motor cortex at the right time and place, increasing motor commands and maximizing movement exactly when required. In a rat model of incomplete SCI that paralyzes one leg, our cortical neuroprosthesis immediately alleviated walking deficits and improved long-term recovery of leg control 1. In the present study, we tested the impact of a bicortical neuroprosthesis in a preclinical cat model of large contusion SCI that paralyzes both legs, as a further step towards human use.

PURPOSE:Clinician-investigators have an important role in the development and implantation of new therapies and treatment modalities; however, there have been several reports highlighting a pending shortage in the clinician-investigators' workforce. In Canada, the Royal College has promoted the development of clinician-investigators programs (CIP) to facilitate the training of these individuals. There is currently a paucity of data regarding the outcomes of such programs. This study aims to identify the strengths and areas of improvement of the Montreal University CIP.  Methods: An internet-based 51-question survey was distributed to all the alumni from the University of Montreal CIP. Participation was voluntary and no incentives were provided. The response rate was 64%.  Results: Among respondents, 50% (n=16) had completed their clinical residency and all CIP requirements. The majority of these individuals (63%) had become independent investigators and had secured provincial and national funding. Satisfaction of the respondents was high regarding the overall program (85%), the research skills developed during the CIP (84%) and the financial support obtained during the program (72%). The satisfaction rate regarding career planning was lower (63%).  Conclusion: This survey demonstrates that, while indicators are favorable, some areas still require improvement. Several steps to improve the CIP have been identified; notably, the transition from the CIP to early independent career has been identified as critical in the development of clinician-investigators and steps have been taken to improve this progression.

Severe traumatic brain injury (TBI), cerebral hemorrhage or cardiac arrest can lead to disorders of consciousness, such as coma, vegetative state and minimally conscious state. Patients usually transition from one state to another in the first months after the neurological event, but some patients remain in vegetative state or minimally conscious state indefinitely. Many groups have reported increased arousal or cognitive performance in these patients following deep brain stimulation (DBS) of the centromedian/parafascicularis complex or related structures. Our aim is to systematically review the clinical and preclinical literature supporting a possible therapeutic benefit of DBS for disorders of consciousness.

ABSTRACT:Introduction:Alzheimer’s disease (AD) cerebrospinal fluid (CSF) biomarkers are promising tools to help identify the underlying pathology of neurocognitive disorders. In this manuscript, we report our experience with AD CSF biomarkers in 262 consecutive patients in a tertiary care memory clinic.Methods:We retrospectively reviewed 262 consecutive patients who underwent lumbar puncture (LP) and CSF measurement of AD biomarkers (Aβ1–42, total tau or t-tau, and p-tau181). We studied the safety of the procedure and its impact on patient’s diagnosis and management.Results:The LP allowed to identify underlying AD pathology in 72 of the 121 patients (59%) with early onset amnestic mild cognitive impairment (aMCI) with a high probability of progression to AD; to distinguish the behavioral/dysexecutive variant of AD from the behavioral variant of frontotemporal dementia (bvFTD) in 25 of the 45 patients (55%) with an atypical neurobehavioral profile; to identify AD as the underlying pathology in 15 of the 27 patients (55%) with atypical or unclassifiable primary progressive aphasia (PPA); and to distinguish AD from other disorders in 9 of the 29 patients (31%) with psychiatric differential diagnoses and 19 of the 40 patients (47%) with lesional differential diagnoses (normal pressure hydrocephalus, encephalitis, prion disease, etc.). No major complications occurred following the LP.Interpretation:Our results suggest that CSF analysis is a safe and effective diagnostic tool in select patients with neurocognitive disorders. We advocate for a wider use of this biomarker in tertiary care memory clinics in Canada.

Rationale: Deep brain stimulation (DBS) of several sites, such as the thalamus, has been shown to reduce seizure frequency and interictal epileptiform activity in patients with refractory epilepsy. Recent findings have demonstrated that the insula is part of the 'rich club' of highly connected brain regions. This pilot study investigated short-term effects of high-frequency (HF) insular DBS on interictal epileptiform discharge (IED) rate in patients with refractory epilepsy. Methods: Six patients with drug-resistant epilepsy undergoing an intracranial electroencephalographic study received two sets of 10 min continuous 150 Hz HF-DBS of the insula. For each patient, epileptiform activity was analyzed for a total of 80 min, starting 20 min prior to stimulation set 1 (S1), and ending 20 min after stimulation set 2 (S2). All IEDs were identified and classified according to their anatomic localization by a board-certified epileptologist. The IED rate during the 20 min preceding S1 served as a baseline for comparison with IED rate during S1, S2 and post-stimulation periods. Results: HF-DBS of the anterior insula (aINS) was performed in a patient with an aINS epileptic focus (patient 1). HF-DBS of the posterior insula (pINS) was performed in two patients with a pINS epileptic focus (patients 2 and 4), in one patient with an aINS focus (patient 3), and in two non-insular patients (patients 5 and 6). The total IED (irrespective of their location) rate significantly decreased (p < 0.01) in two patients (patients 1 and 2) during the stimulation period, whereas it significantly increased (p < 0.01) in one patient (patient 6); there was no change in the other three patients. Looking at subsets of spike localization, HF-DBS of the aINS significantly reduced aINS and orbitofrontal IEDs in patient 1 (p < 0.01), while HF-DBS of the pINS had an effect on pINS IEDs (p < 0.01) in both patients with a pINS focus; there was no significant effect of HF-DBS of the insula on IEDs in temporal or other frontal regions. Conclusion: Short-term HF-DBS of the insula had heterogeneous effects on the IED rate. Further work is required to examine factors underlying these heterogeneous effects, such as stimulation frequency, location of IEDs and subregions of the insula stimulated.

BACKGROUND:Hajdu-Cheney syndrome (HCS) is a rare connective tissue disorder characterized by severe bone demineralization. In the spine, it is associated with the early onset of severe osteoporosis and can cause spondylolisthesis. Spinal instrumentation in the setting of severe osteoporosis is challenging because of poor resistance of vertebrae to biomechanical stress.OBSERVATIONS:A 59-year-old woman with known idiopathic HCS presented with a grade 4 L5-S1 spondylolisthesis and right L5 pedicle fracture associated with a left L5 pars fracture, causing a progressive L5 radiculopathy that was worse on the left side than the right side and bilateral foot drop. The authors performed decompressive lumbar surgery, which included a complete L5 laminectomy and resection of the left L5 pedicle. This was followed by multilevel lumbosacral instrumentation using cement-augmented fenestrated pedicle screws as well as transdiscal sacral screws and bilateral alar-iliac fixation. Postoperatively, the radicular pain resolved, and the left foot drop partially recovered.LESSONS:Stabilization of high-grade spondylolisthesis in the setting of bone demineralization disorders is challenging. The use of different instrumentation techniques is important because it increases biomechanical stability of the overall instrumentation construct.

INTRODUCTION: Hemispherectomy and its modern variants are effective surgical treatments for medically intractable unihemispheric epilepsy. While complications of hemispherectomy such as postoperative hydrocephalus are well documented, a less-studied phenomenon of postoperative midline brain shift (MLBS) has only been described anecdotally and never formally studied. METHODS: A retrospective review of consecutive pediatric patients who underwent hemispherectomy for medically refractory epilepsy at UCLA between 1994 and 2018 was performed. Patients were stratified by severity of MLBS, shunt placement, type of shunt valve, and opening pressure. MLBS progression was evaluated within groups using repeated measures ANOVA and compared between groups using ANCOVA while adjusting for follow-up time and baseline postoperative MLBS. RESULTS: In total, 97 patients with a median follow-up of 17.7 months were analyzed in this study. Of these patients, 27 (28%) required CSF diversion via shunt placement in the ipsilateral cavity for post-hemispherectomy hydrocephalus. In non-shunted patients, average MLBS immediately following hemispherectomy and at last follow-up was 4.8 ± 4.7 and 8.3±6.4 mm, respectively. In shunted patients, average MLBS immediately after hemispherectomy and at latest follow-up following shunt placement was 6.5 ± 3.3 and 14.6 ± 9.5 mm, respectively. MLBS increased for both shunted and non-shunted patients between first and last follow-up. However, MLBS progression between first and last follow-up was significantly greater in the shunted cohort than the non-shunted cohort [F (1,92) = 5.33, p = 0.023]. Placement of valves with higher opening pressure settings did not significantly increase MLBS relative to non-shunted patients [F (1,73) = 0.1, p = 0.765], whereas MLBS was significantly greater with low opening pressure settings [F (1,85) = 8.5, p = 0.004]. Furthermore, severe MLBS was significantly associated with debilitating headaches (p = 0.042). CONCLUSION: Patients undergoing hemispherectomy often develop postoperative MLBS. The progression of MLBS is significantly exacerbated by CSF shunting of the ipsilateral post-surgical cavity, specifically when accomplished with lower opening pressure settings. Severe MLBS is associated with severe headaches, suggesting that MLBS exacerbation may be related to overshunting.

BACKGROUND: Hemispherectomy and its modern variants are effective surgical treatments for medically intractable unihemispheric epilepsy. Although some complications such as posthemispherectomy hydrocephalus are well documented, midline brain shift (MLBS) after hemispheric surgery has only been described anecdotally and never formally studied. OBJECTIVE: To assess the natural history and clinical relevance of MLBS and determine whether cerebrospinal fluid (CSF) shunting of the ipsilateral surgical cavity exacerbates MLBS posthemispheric surgery. METHODS: A retrospective review of consecutive pediatric patients who underwent hemispheric surgery for intractable epilepsy and at least 6 months of follow-up at UCLA between 1994 and 2018 was performed. Patients were grouped by MLBS severity, shunt placement, valve type, and valve opening pressure (VOP). MLBS was evaluated using the paired samples t-test and analysis of covariance adjusting for follow-up time and baseline postoperative MLBS. RESULTS: Seventy patients were analyzed, of which 23 (33%) required CSF shunt placement in the ipsilateral surgical cavity for posthemispherectomy hydrocephalus. MLBS increased between first and last follow-up for nonshunted (5.3 ± 4.9-9.7 ± 6.6 mm, P < .001) and shunted (6.6 ± 3.5-16.3 ± 9.4 mm, P < .001) patients. MLBS progression was greater in shunted patients (P = .001). Shunts with higher VOPs did not increase MLBS relative to nonshunted patients (P = .834), whereas MLBS increased with lower VOPs (P = .001). Severe MLBS was associated with debilitating headaches (P = .048). CONCLUSION: Patients undergoing hemispheric surgery often develop postoperative MLBS, ie, exacerbated by CSF shunting of the ipsilateral surgical cavity, specifically when using lower VOP settings. MLBS exacerbation may be related to overshunting. Severe MLBS is associated with debilitating headaches.

BACKGROUND:Rupture of spinal aneurysms is a rare cause of subarachnoid hemorrhage. These aneurysms are often associated with a variety of vascular malformations that increase blood flow in the spinal circulation or with disorders that compromise the vessel wall. However, spinal aneurysms may be isolated, not associated with any known predisposing condition. The objective of this study is to explore the possible mechanisms associated with the formation and rupture of isolated spinal aneurysms (ISAs).METHODS:We conducted a retrospective review of a series of consecutive patients admitted for a ruptured ISA. In all cases, spinal angiography confirmed the presence of a spinal aneurysm responsible for the bleeding. Particular attention was paid to medical history and symptoms before bleeding, for potential factors predisposing to their formation and rupture.RESULTS:Between 2008 and 2020, ten cases of spinal aneurysms were seen at our institution including 4 cases of ISA. All patients with ISA were female, and in 3 cases the aneurysm involved the territory of the posterior spinal artery. In 3 of these 4 (75%) ISA cases, there was a strikingly similar history of retching and vomiting preceding the thunderclap headache. In 1 patient, the aneurysm was surgically resected; pathologic analysis revealed a fusiform dissecting aneurysm. All 4 patients had a favorable outcome.CONCLUSIONS:We suggest that the straining during prolonged retching and vomiting plays a role in the formation and rupture of some ISAs, possibly because of pressure spikes, increased transmural arterial pressure, and increased wall shear stress during straining.

INTRODUCTION:To date, clinical trials of deep brain stimulation (DBS) for refractory chronic pain have yielded unsatisfying results. Recent evidence suggests that the posterior insula may represent a promising DBS target for this indication.METHODS:We present a narrative review highlighting the theoretical basis of posterior insula DBS in patients with chronic pain.RESULTS:Neuroanatomical studies identified the posterior insula as an important cortical relay center for pain and interoception. Intracranial neuronal recordings showed that the earliest response to painful laser stimulation occurs in the posterior insula. The posterior insula is one of the only regions in the brain whose low-frequency electrical stimulation can elicit painful sensations. Most chronic pain syndromes, such as fibromyalgia, had abnormal functional connectivity of the posterior insula on functional imaging. Finally, preliminary results indicated that high-frequency electrical stimulation of the posterior insula can acutely increase pain thresholds.CONCLUSION:In light of the converging evidence from neuroanatomical, brain lesion, neuroimaging, and intracranial recording and stimulation as well as non-invasive stimulation studies, it appears that the insula is a critical hub for central integration and processing of painful stimuli, whose high-frequency electrical stimulation has the potential to relieve patients from the sensory and affective burden of chronic pain.

BACKGROUND/AIMS:The logopenic variant of primary progressive aphasia (lvPPA) is characterized by impaired word-finding and sentence repetition with phonologic errors but spared motor speech and grammar and semantic knowledge. Although its language deficits have been well studied, the full spectrum of cognitive changes in the lvPPA remains to be defined. We aimed to explore the neurocognitive profile of the lvPPA using a newly developed cognitive screening tool for atypical dementias, the Dépistage Cognitif de Québec (DCQ).METHODS:We compared 29 patients with lvPPA to 72 amnestic variant Alzheimer disease (aAD) to 438 healthy control (HC) participants. Performance on the 5 indexes of the DCQ (Memory, Visuospatial, Executive, Language and Behavioral) was compared between the 3 groups.RESULTS:Results showed a significantly lower performance for lvPPA participants in all neurocognitive domains, when compared to HC. When compared to aAD, lvPPA participants had significantly lower scores for language, executive, and visuospatial abilities, but not for memory and behavior.CONCLUSION:Altogether, these findings better define the neurocognitive changes of lvPPA.

Background: Hypometabolism of the posterior cingulate cortex (PCC) is an important diagnostic feature of late-onset, amnestic Alzheimer’s disease (AD) measured with 18F-fluorodeoxyglucose positron emission tomography (FDG-PET). However, it is unclear whether PCC hypometabolism has diagnostic value in young-onset, non-amnestic variants of AD, which exhibit less pathology in the hippocampus and default mode network. Objective: Evaluate the prevalence and diagnostic value of PCC hypometabolism in non-amnestic variants of AD. Methods: We retrospectively identified 60 patients with young-onset, atypical dementia who have undergone a detailed clinical evaluation, FDG-PET, and an amyloid biomarker (amyloid-PET or cerebrospinal fluid analysis). We quantitatively analyzed regional hypometabolism in 70 regions of interest (ROI) using the MIMneuro® software. Results: Based on a cut-off of z-score < –1.5 for significant PCC hypometabolism, the prevalence of PCC hypometabolism in non-amnestic variants of AD was 65% compared to 28% in clinical variants of frontotemporal dementia (FTD). The ROI with the maximal hypometabolism was the dominant middle temporal gyrus in the language variant of AD (mean z score –2.28), middle occipital gyrus in PCA (–3.24), middle temporal gyrus in frontal AD (–2.70), and angular gyrus in corticobasal syndrome due to AD (–2.31). The PCC was not among the 10 most discriminant regions between non-amnestic variants of AD versus clinical variants of FTD. Conclusion: We conclude that PCC hypometabolism is not a discriminant feature to distinguish non-amnestic variants of AD from clinical variants of FTD—and should be interpreted with caution in patients with young-onset, non-amnestic dementia.

INTRODUCTION:It is well known that some patients with Alz-heimer's disease (AD) have atypical, nonamnestic presentations. While logopenic aphasia and posterior cortical atrophy are well-characterized atypical variants of AD, the behavioral/dysexecutive variant remains a controversial entity, lacking consensus regarding its distinctive clinical and imaging features.METHODS:We present a case series of 8 patients with biomarker confirmation of AD (cerebrospinal fluid [CSF] analysis or amyloid positron emission tomography [PET]) and a progressive frontal syndrome, defined as prominent behavioral and/or executive deficits at initial presentation. We characterize the cohort based on clinical features, cognitive performance in 4 domains (memory, visuospatial, executive, and language) as well as behavior on the Dépistage Cognitif de Québec (DCQ), and regional brain metabolism using 18F-fluorodeoxyglucose PET (FDG-PET). We compare these features with 8 age-matched patients diagnosed with the behavioral variant of frontotemporal dementia (bvFTD) and 37 patients with typical amnestic AD.RESULTS:Patients with the behavioral/dysexecutive variant of AD presented with early-onset (mean age: 59 years old) progressive executive and behavioral problems reminiscent of bvFTD, including disinhibition, loss of social conventions, and hyperorality. Patients scored higher on the Memory Index and lower on the Behavioral Index than patients with amnestic AD on the DCQ, yet they were indistinguishable from patients with bvFTD on each of the cognitive indices. Visual analysis of FDG-PET revealed half of patients with behavioral/dysexecutive AD presented with frontal hypometabolism suggestive of bvFTD and only 3/8 (37.5%) presented significant hypometabolism of the posterior cingulate cortex. Group-level analysis of FDG-PET data revealed that the most hypometabolic regions were the middle temporal, inferior temporal, and angular gyri in behavioral/dysexecutive AD and the inferior frontal gyrus, anterior cingulate cortex, caudate nucleus, and insula in bvFTD.CONCLUSION:The behavioral/dysexecutive variant of AD is a rare, atypical young-onset variant of AD defined clinically by early and prominent impairments in executive and behavioral domains. While behavioral/dysexecutive AD is hardly distinguishable from bvFTD using clinical and cognitive features alone, CSF biomarkers and temporoparietal hypometabolism help predict underlying pathology during life.