Cerebral Peduncle Research Articles

An Endless Relay of Words: Syndrome of Frontal-like Disinhibition and Logorrhea following a Thalamic Hemorrhagic Stroke (P4-12.004)

<h3>Objective:</h3> Na <h3>Background:</h3> 66-year-old right-handed female who presented after acute-onset behavioral changes starting five days prior. Although anosognosic to these changes, family endorsed sudden onset personality changes accompanied by insomnia, headache, and disinhibition in the form of profuse logorrhea. No focal neurological symptoms were reported at onset or following the episode. After a psychiatric evaluation revealed no psychiatric pathology to which the symptoms could be attributed, neurological consultation was recommended to assess for an organic etiology. <h3>Design/Methods:</h3> Na <h3>Results:</h3> Mental status examination showed an alert and oriented female that demonstrated intact language and memory faculties, albeit being profusely logorrheic and circumstantial in her speech patterns. Her neurological examination was normal. CT Head without contrast demonstrated an incidental 1.3 cm right thalamic hemorrhage. MRI of the brain confirmed right thalamic hemorrhage, in addition to mild surrounding vasogenic edema extending to the right cerebral peduncle; no microhemorrhages were noted on gradient-echo or susceptibility weighted images (cortical or otherwise). MR Angiogram did not show any vascular abnormalities. MR Perfusion did not show any hemodynamic changes. <h3>Conclusions:</h3> Despite hemorrhagic strokes of the thalamus secondary to chronic hypertension being a common entity, purely behavioral manifestations as their sole symptomatic expression are relatively uncommon. The thalamus is schematically understood as the nervous system’s relay center mediating functions from the sensorimotor to the cognitive-behavioral. Numerous pathways exist in a multitude of orientations, from unidirectional to reciprocal and from diffuse to specific, providing orderly chaos to neurological input-output circuits. Amongst its nuclei, the medio-dorsal nuclei of the thalamus seem to be most intimately interconnected with the prefrontal cortices via thalamocortical connections that radiate to the ventrolateral prefrontal cortices, the dorsolateral prefrontal cortices and, most relevant to this discussion, the orbitofrontal cortices. This suggests a possible deep brain substrate for a frontal-like disinhibition syndrome in the absence of cortical or fascicular damage. <b>Disclosure:</b> Dr. Falero Pomales has nothing to disclose. Dr. Wadood has nothing to disclose. Dr. Etter has nothing to disclose.

Stroke Like Presentation Of CNS Lymphoma (P14-13.005)

<h3>Objective:</h3> To present an unusual case of primary diffuse large B-cell lymphoma of the CNS with stroke-like symptoms, imaging findings and anti-phospholipid antibodies. <h3>Background:</h3> Primary diffuse large B-cell lymphoma of the central nervous system is a rare primary tumor of the brain, that is challenging to diagnose. <h3>Design/Methods:</h3> Case and literature review. <h3>Results:</h3> A 56-year-old man with hypertension, hyperlipidemia, and diabetes presented with acute onset L sided weakness with right midbrain, cerebral peduncle and thalamic increase DWI signal and antiphospholipid antibodies, initially suspected for possible stroke. Close follow up imaging with contrast study was planned due to atypical imaging findings. Patient was discharged to acute rehab on therapeutic Warfarin. Two weeks later, he returned with poor mental status, worsening left sided weakness, numbness, dysarthria and apathy. Repeat MRI brain showed increased DWI signal with increased mass effect. Post contrast MRI brain revealed expansile infiltrative FLAIR and DWI hyperintensity in the right thalamocapsular region extending into the midbrain and anterior cerebellum with superimposed patchy enhancement in the right thalamocapsular area. Findings are suspicious of CNS lymphoma vs high-grade glioma vs inflammatory and infectious processes. Lumbar puncture was non-revealing. A right thalamic biopsy confirmed neoplastic B-cells, positive for Bcl-2, subset Bcl-6 (50%) and MUM-1 (50%), negative for CD10, CD30, and Bcl-, compatible with primary diffuse large B-cell lymphoma of CNS. Immediate treatment with R-MPV regimen (rituximab, methotrexate, procarbazine, vincristine) was started, in addition to solumedrol and whole brain radiation therapy with rapid clinical improvements after steroids treatment before combination chemotherapy. <h3>Conclusions:</h3> Primary CNS lymphoma is a rare and elusive disorder with variable symptoms, signs, clinical courses and images findings that can mimic stroke syndromes and requires vigilance and close follow up for accurate diagnosis and effective treatment. Hypercoagulable state or antiphospholipid antibodies can be associated with large B cell lymphoma. <b>Disclosure:</b> Dr. Sawass Najjar has nothing to disclose. The institution of Dr. Wang has received research support from Maimonides Research &amp; Development Foundation.

Cryoglobulinemia and Neuromyelitis optica: a case of progressive weakness and neurocognitive decline (P10-5.026)

<h3>Objective:</h3> Describe a case of a woman with mixed cryoglobulinemia who presented with progressive weakness and biopsy proven systemic vasculitis in the setting of Hepatitis C virus (HCV) negative serology. <h3>Background:</h3> The disease expression of mixed cryoglobulinemia vasculitis caused by HCV infection triggers the downstream B-cell arm of autoimmunity. <h3>Design/Methods:</h3> A 61 year old woman with a history of HCV infection, mixed cryoglobulinemia, mononeuritis multiplex secondary to nervous system vasculitis affecting peripheral nerves and hypertension presented with weakness that progressed to quadriparesis and neurocognitive decline over a period of eight months. <h3>Results:</h3> MRI examination of the brain showed bilateral ventral pontine lesions extending into the middle cerebellar peduncles, ventrolateral midbrain and cerebral peduncles as well as bilateral cortical frontal lobe lesions. Also present were intrinsic mixed intensity DWI/ADC lesions of undetermined etiology and extensive subcortical and periventricular white matter hyperintensities. CT angiography of her head and neck showed large vessel intracranial vasculopathy involving the bilateral MCA branches. Conventional angiogram, however, did not show any evidence of angiographic vasculitis. MRI spectroscopy was non-diagnostic. MRI of the neuroaxis showed a small focus of linear non-enhancing hyperintense lesion at the level of C3. EMG demonstrated severe generalized sensory-motor polyneuropathy with severe axonal loss. EEG showed mild to moderate diffuse slowing. CSF evaluation was negative, HCV viral load was undetectable, connective tissue markers (Anti-dsDNA, Anti-SCL70, Anti-CENTR, Anti-RNP, Anti-Smith, Anti-SSA/SSB, ANCA) were negative and the remaining serology was significant for elevated ESR, CRP, low C4 complements, positive anti-AQP4 antibodies titers (1:2560) and positive myelin basic protein. Brain biopsy showed perivascular lymphocytic inflammation, confirming vasculitis. Our patient completed courses of high dose steroids, IVIG and Rituximab with mild improvement in motor strength. <h3>Conclusions:</h3> Although an atypical feature of NMO, cryoglobulinemia with production of anti-AQP4 antibodies may, in part, contribute to development of a demyelinating process. <b>Disclosure:</b> Dr. Esechie has nothing to disclose. Dr. Harazeen has nothing to disclose. Dr. Rivera Vega has nothing to disclose. Dr. Thottempudi has nothing to disclose. Dr. Chhabra has stock in Pfizer. Dr. Chhabra has stock in Biogen. Dr. Chhabra has stock in Johnson and Johnson. Dr. Chhabra has stock in Medtronic. Dr. Shaltoni has nothing to disclose. Muhammad Zeeshan Memon, MD has nothing to disclose. Dr. Patel has nothing to disclose. Dr. Wu has nothing to disclose.

Acute Fulminant Encephalitis in the Setting of Acute COVID-19 Infection (P12-3.008)

<h3>Objective:</h3> NA <h3>Background:</h3> Encephalitis in the setting of COVID-19 has been reported, however the mechanism by which SARS-CoV-2 causes encephalitis remains unclear. We aimed to describe a case of fulminant limbic encephalitis associated with acute COVID-19 infection. <h3>Design/Methods:</h3> NA <h3>Results:</h3> A 33-year-old COVID-19 positive female presented after being found unresponsive with seizure-like activity. On arrival, patient was comatose with intermittent left gaze deviation, weak gag and cough reflexes, and no movement to pain. She was intubated for airway protection (without hypoxia). Continuous EEG demonstrated generalized and bilaterally independent epileptiform discharges, with no electrographic or clinical seizures. Patient was prophylactically started on levetiracetam. Brain MRI revealed scattered DWI and T2 hyperintensities involving supratentorial and infratentorial areas more prominent in temporal lobes. CSF analysis showed mild neutrophilic pleocytosis; protein and glucose were normal. Infectious, autoimmune, and paraneoplastic encephalopathy in CSF/serum panels were negative. CSF COVID-19 PCR was negative. ESR, CRP and ferritin were mildly elevated. High-dose steroids and intravenous immunoglobulin were initiated. After 7 days repeated brain MRI demonstrated progression of T2 hyperintensities including midbrain, cerebral peduncles, and right hemispheric cortical ribboning. Patient continued to decline with gradual loss of brainstem reflexes and downward gaze deviation with ocular bobbing movements. Due to clinical deterioration the patient was transitioned to comfort care and deceased after extubating. <h3>Conclusions:</h3> There have been increasing reports of severe encephalitis subtypes among younger COVID-19 patients commonly associated with poor outcomes compared to other subtypes of encephalitis. To our knowledge this is the first case of encephalitis associated with COVID-19 infection with no response to immunomodulatory therapies. Other possible etiologies in this case include hypoxic injury, hypoglycemia, or toxic insults, which were considered less likely given clinical scenario. In our case, PCR of CSF was negative for COVID-19 which raises possibility of secondary hyperinflammation or molecular mimicry as potential causes. <b>Disclosure:</b> Dr. Kherallah has nothing to disclose. Dr. Manrique has nothing to disclose. Dr. Vennavaram has nothing to disclose. Dr. Samaha has nothing to disclose.

Iron Deficiency Anemia and Ischemic Stroke in Premenopausal Women (P14-5.022)

<h3>Objective:</h3> We describe three young women with iron deficiency anemia who developed ischemic strokes in the absence of typical risk factors. <h3>Background:</h3> Ischemic stroke is the third leading cause of death in women. Women have unique risk factors for ischemic stroke. Iron deficiency anemia disproportionately affects premenopausal women and has previously been identified to be associated with ischemic stroke. <h3>Design/Methods:</h3> N/A <h3>Results:</h3> A 39-year old woman with hypertension and menorrhagia presented with left leg weakness and dizziness. Labs revealed a hemoglobin of 5.9g/dL, a unremarkable hypercoagulable work up, transesophageal echo, urine toxicology, rheumatological evaluation, and MRA brain vessel wall imaging. An ultrasound of her uterus revealed a pelvic fibroid measuring 6.5cm and MRI brain revealed a small right anterior cerebral artery territory infarction. A 46-year-old woman with chronic iron deficiency anemia with a hemoglobin of 6.8g/dL who presented with left mild sided weakness and was found to have a right MCA M3 occlusion by CT angiography of the head. She received intravenous tenecteplase and underwent decompressive craniectomy for a right temporal infarct associated with cerebral edema seen on MRI brain. Investigations revealed a normal hemoglobin electrophoresis, urine toxicology, hypercoagulable evaluation, rheumatological evaluation and transesophageal echo. A 43 year old woman presented with diplopia secondary to a vertical gaze palsy. MRI brain revealed an infarct in the left thalamus, cerebral peduncle, and midbrain. Cerebral angiography, transesophageal echocardiogram, urine toxicology, rheumatological evaluation, and hypercoagulable work up were unremarkable. Hemoglobin was 7.2g/dL on presentation and an EGD revealed an antral and duodenal ulcer. All three patients received packed RBC transfusions, iron replacement therapy and discontinuation of aspirin until hemoglobin stabilized. <h3>Conclusions:</h3> Iron deficiency anemia may be an important yet under-recognized risk factor for acute ischemic stroke and should be treated aggressively in premenopausal women. Further studies are warranted. <b>Disclosure:</b> Dr. Imam has nothing to disclose. Dr. Salahuddin has nothing to disclose.

Atypical Presentation of Nocardia Brainstem Abscess: A Case Report (P1-10.006)

<h3>Objective:</h3> NA <h3>Background:</h3> Roughly 1–2% of cerebral abscesses are caused by <i>Nocardia spp.</i> and usually occur in immunocompromised patients. Mortality of <i>Nocardia</i> is around three times higher than other bacterial abscesses, making early diagnosis critical. Lesions are usually supratentorial and multiloculated due to daughter abscesses. <h3>Design/Methods:</h3> NA <h3>Results:</h3> A healthy 70-year-old male with history of diabetes mellitus and hypertension presented with new onset right upper extremity weakness, right-sided facial droop, and expressive aphasia. Brain MRI revealed an enhancing left-sided pontine mass with surrounding vasogenic edema. Lumbar puncture was obtained which was remarkable for leukocytosis, monocyte predominance (WBC 13thou/cmm). Cultures and PCR of cerebrospinal fluid were negative with no bacterial or fungal growth. He was started on intravenous steroids with improvement in his symptoms and discharged with close follow up. Three days later, he returned with worsening right upper arm weakness. Repeat MRI brain showed an expanding mass at the left aspect of the brainstem extending into the cerebral peduncle and medulla oblongata. MR spectroscopy favored abscess formation over metastasis or hematoma, and the patient was started on intravenous ampicillin empirically for presumed Neurolisteriosis. As the patient experienced only minimal neurologic and radiologic improvement after two weeks, the decision for surgical biopsy was pursued. Left retromastoid craniotomy was performed and cultures grew <i>Nocardia cyriacigeorgica</i>, and the patient was started on trimethoprim-sulfamethoxazole, imipenem and amikacin. <h3>Conclusions:</h3> While <i>Nocardia</i> CNS infections are typically supratentorial lesions, we present an atypical presentation of a patient who presented with progressive neurologic deficits from an expanding pontine mass. <i>Nocardia</i> abscesses are extremely rare and usually present in immunocompromised hosts. Despite being healthy with no significant prodrome prior to presentation, our patient had radiologic evidence of cirrhotic liver morphology which may have predisposed him to infection. This case highlights that <i>Nocardia</i> should be considered as an infectious agent in brainstem abscesses. <b>Disclosure:</b> Dr. Shastry has nothing to disclose. Mr. Sacks has nothing to disclose. Dr. Reyes has nothing to disclose. Dr. Su has nothing to disclose. Dr. Clauser has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Bigoen . The institution of Dr. Clauser has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Genzyme. Dr. Clauser has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Genentech . Dr. Clauser has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for Genzyme. Dr. Clauser has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for Biogen. Dr. Clauser has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for Novartid. Dr. Benjamin has nothing to disclose.

Evidence of Sympathetic Overactivity in Subjects with REM Behavior Disorder at Risk for Parkinson’s Disease (P6-13.002)

<h3>Objective:</h3> To evaluate sympathetic nervous system (SNS) activity in subjects with REM sleep behavior disorder (RBD) at risk of Parkinson’s disease, using imaging and autonomic functions markers. <h3>Background:</h3> While the nature of RBD is not completely understood, there is evidence that enhancement of noradrenergic activity may play a causative role, as suggested by evidence of persistent tonic discharge of locus coeruleus (LC) and RBD-triggering action of selective norepinephrine reuptake inhibitors. <h3>Design/Methods:</h3> Subjects &gt;50 years old with RBD with at least one pre-motor PD symptom (hyposmia, constipation, depression) were tested with a battery of autonomic evaluations including SCOPA-AUT questionnaire, cardiac MIBG scintigraphy, Heart Rate Variability (HRV) and neuromelanin sensitive MRI (NSMRI) of LC and substantia nigra (SN). Analyzed variables included: 1) for MIBG, late heart/mediastinum (H/M) ratio and washout ratio (WR); 2) for HRV, time and frequency domain measures; 3) for NSMRI, contrast-to-noise ratio (CNR) between LC and pons and between substantia nigra (SN) and cerebral peduncles. Results were compared with available normative ranges. <h3>Results:</h3> 14 subjects (11M, age 66.2±8.2) were enrolled. Average total SCOPA-AUT score was increased (12.1±6.7 vs 8.8±5.4), with gastrointestinal (2.4±2.1 vs 1.4±1.6), urinary (5.4±2.7 vs 3.9±2.4) and cardiovascular (0.86±1.10 vs 0.3±0.6) scores above normal ranges. MIBG late H/M ratio was reduced (1.45±0.31) with increased WR (33.0±14.8). HRV results showed enhanced sympathetic and low parasympathetic activity both in time (SDNN 106.8±73.2ms; RMSSD 21.9±10.9ms; PNN50% 6.7±8.4%) and frequency domain (LF/HF 3.4±1.8). NMSMRI showed high LC CNR (right 3.26±1.9 vs 2.08±0.5; left 2.95±0.9 vs 2.79±0.5). SN CNR was high (Medial 6.24±1.9 vs 4.57±0.8; Central 6.26±1.6 vs 3.43±0.6; Lateral 3.44±2.1 vs 3.05±0.5) and MDS-UPDRS motor scores were low (2.9±3.3). <h3>Conclusions:</h3> RBD subjects at risk for PD show abnormal autonomic scores, which appears to be driven by SNS overactivity, as suggested by increased MIBG WR, elevated LF/HF HRV ratios and increased LC and SN NSMRI signal. <b>Disclosure:</b> Dr. Tagliati has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Abbott. Dr. Tagliati has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Boston Scientific. Dr. Tagliati has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Supernus. Dr. Tagliati has received personal compensation in the range of $500-$4,999 for serving as a Consultant for NeuroDerm. Dr. Tagliati has received publishing royalties from a publication relating to health care. Dr. Gregorio has nothing to disclose. Dr. Maghzi has nothing to disclose. Gloria Obialisi has nothing to disclose. Dr. Hogg has nothing to disclose. Dr. Malatt has nothing to disclose. Dr. Tan has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Allergan. Dr. Artal has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Jazz Pharmaceuticals. Dr. Artal has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Private Parties. The institution of Dr. Artal has received research support from Jazz Pharma. The institution of Dr. Artal has received research support from Axsome. The institution of Dr. Artal has received research support from Suven. Dr. Shehata has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Abbott. Brian Renner has nothing to disclose. The institution of Dr. Sati has received research support from National Multiple Sclerosis Society. The institution of Dr. Sati has received research support from National Institutes of Health. Dr. Sati has received publishing royalties from a publication relating to health care.

HSV-2 Retinitis and Encephalitis Masquerading as Giant Cell Arteritis and Acute Ischemic Stroke of the Midbrain (P12-10.002)

<h3>Objective:</h3> To describe a unique case of stroke mimicry. <h3>Background:</h3> Non-vascular causes of acute neurological symptoms may clinically and radiographically mimic ischemic strokes. In the brainstem, such considerations are generally restricted to neoplastic, demyelinating, or infectious etiologies. HSV-2 may very rarely cause isolated mesencephalitis. <h3>Design/Methods:</h3> We describe a patient who presented with headache, arthralgias, and visual dysfunction who was initially diagnosed with giant cell arteritis (GCA) but was eventually found to have HSV-2 infection. <h3>Results:</h3> A 75-year-old man with past medical history notable for atrial fibrillation (on apixaban), hypertension, hyperlipidemia, and rheumatoid arthritis (on adalimumab) presented for evaluation of gait instability. Four weeks prior to presentation, he developed bitemporal headaches without visual symptoms and arthralgias. His rheumatologist checked an ESR (40) and ordered a temporal artery biopsy. He presented the day his apixaban was held prior to biopsy (1 week prior to this presentation) with right eye inferior visual field loss. Fundoscopy revealed disc edema felt consistent with anterior ischemic optic neuropathy. He was treated with pulse-dose steroids out of concern for GCA and underwent bilateral temporal artery biopsy before being discharged home on an oral steroid taper and resumed anticoagulation. CT, CTA, and MRI were reportedly normal and the biopsies were ultimately negative. He then presented this admission with gait instability and MRI exhibited a diffusion restricting lesion with T2-FLAIR hyperintensity without hemorrhage in the left cerebral peduncle. His visual symptoms progressed and he underwent right eye anterior chamber paracentesis with fluid resulting PCR positive for HSV-2. Subsequent CSF sampling also revealed lymphocytic pleocytosis and HSV-2 positivity. Despite maximal medical therapy, he lost vision in both eyes over a matter of weeks before developing Charles-Bonnet syndrome. <h3>Conclusions:</h3> HSV-2 encephalitis may cause mesencephalic, non-hemorrhagic, restricting lesions mimicking acute ischemic stroke. HSV may also cause a necrotizing retinitis, initially mimicking ischemic, even arteritic, optic neuropathy. <b>Disclosure:</b> Dr. Sutherland has received personal compensation in the range of $0-$499 for serving as a Consultant for McGraw-Hill. Dr. Gummerson has nothing to disclose. Dr. De Havenon has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Integra. Dr. De Havenon has stock in Certus. The institution of Dr. De Havenon has received research support from NIH/NINDS. The institution of Dr. De Havenon has received research support from Regeneron Pharmaceuticals. The institution of Dr. De Havenon has received research support from AMAG Pharmaceuticals. The institution of Dr. De Havenon has received research support from AMGEN. Dr. De Havenon has received publishing royalties from a publication relating to health care.

Clinical and Pathological Characterization of VPS16 Dystonia (P11-11.005)

<h3>Objective:</h3> To expand the clinical, radiologic and pathologic understanding of VPS16 related dystonia. <h3>Background:</h3> Variants in VPS16 have been associated with isolated dystonia in 35 cases from Chinese and European cohorts, including report of brainstem signal change on MRI. <h3>Design/Methods:</h3> We describe clinical features in 10 additional individuals with isolated dystonia and VPS16 variants, including neuroimaging on a subset and pathology in one, and perform pooled analysis with published cases. <h3>Results:</h3> 80% were men, mean age onset was 14.1 years (range 5–30), and mean age at exam was 35.89 years (range 11–73). Four began with arm, 3 with leg, and 3 with neck dystonia. Only one remained focal (arm); others became generalized (7), multifocal (1) or segmental (1). Brachial involvement was present in 90%, with 80% crural, 70% cranial/bulbar, and 50% cervical involvement. Two individuals underwent deep brain stimulation and one thalamotomy. Four cases were related, and five others had family history. MRI was available in two cases and demonstrated red nucleus and cerebral peduncle T2 hypointensity. Neuropathologic evaluation in one case (post bilateral GPi DBS) demonstrated asymmetric severe gliosis and marked neuronal loss of the left subthalamic nucleus with optically empty vacuoles and much less right-sided involvement. Pooled analysis with 34 additional published cases showed 62.22% male and average onset of 14.53 years (range 3–50). Onset site was 20.45% cranial/bulbar, 54.55% limb, and 36.36% axial (cervical or trunk); 75% of cases exhibited cranial/bulbar symptoms, 90.9% limb and 81.82% axial involvement. <h3>Conclusions:</h3> Expansion of known cases of VPS16 dystonia further support that it is a childhood-or adolescent-onset disorder, typically with limb or cervical onset that often spreads to the arm and leg. Additional histopathologic and metabolomic evaluation is underway to better understand the lysosomal and endolysosomal pathophysiology that may contribute to both vacuolization in the subthalamic nucleus as well as T2 brainstem hypointensities. <b>Disclosure:</b> The institution of Dr. Pullman has received research support from Empire Clinical Research Investigator Program. The institution of Ms. Raymond has received research support from NIH. Dr. Molofsky has nothing to disclose. Dr. Lubarr has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for applied therapeutics. Dr. Leaver has nothing to disclose. Roberto Ortega has nothing to disclose. Ms. Rawal has nothing to disclose. The institution of Dr. Bennett has received research support from Prevail. Mr. Bushnik has nothing to disclose. Dr. Khorsandi has nothing to disclose. Fedor Panov has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for neuropace. Fedor Panov has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for zimmer biomet. Jean Paul Vonsattel has nothing to disclose. The institution of Dr. Ozelius has received research support from NIH. Dr. Ozelius has received intellectual property interests from a discovery or technology relating to health care. The institution of Dr. Saunders-Pullman has received research support from NIH, Bigglesworth Family Foundation, Empire Clinical Research Investigatory Program. The institution of Dr. Bressman has received research support from Michael J Fox Foundation . The institution of Dr. Bressman has received research support from NIH .

Enhanced Integrity of White Matter Microstructure in Mind–Body Practitioners: A Whole-Brain Diffusion Tensor Imaging Study

Tai Chi Chuan (TCC) is an increasingly popular multimodal mind-body practice with potential cognitive benefits, yet the neurobiological mechanisms underlying these effects, particularly in relation to brain white matter (WM) microstructure, remain largely unknown. In this study, we used diffusion tensor imaging (DTI) and the attention network test (ANT) to compare 22 TCC practitioners and 18 healthy controls. We found extensive differences in fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) between the two groups. Specifically, TCC practitioners had significantly different diffusion metrics in the corticospinal tract (CST), fornix (FX)/stria terminalis (ST), and cerebral peduncle (CP). We also observed a significant correlation between increased FA values in the right CP and ANT performance in TCC practitioners. Our findings suggest that optimized regional WM microstructure may contribute to the complex information processing associated with TCC practice, providing insights for preventing cognitive decline and treating neurological disorders with cognitive impairment in clinical rehabilitation.

Effect of Enlarged Perivascular Spaces in Reliable Distinction of Prospective Targeting During Deep Brain Stimulation in Patients With Advanced Parkinson's Disease: A Study of Deterministic and Probabilistic Tractography.

Precise electrode position is vital for effective deep brain stimulation in treating motor symptoms in Parkinson's disease (PD). Enlarged perivascular spaces (PVSs) are associated with pathophysiology of neurodegenerative diseases including PD and may affect the microstructure of surrounding brain tissue. To quantify the clinical implications of enlarged PVS on tractography-based stereotactic targeting in patients with advanced PD selected to undergo deep brain stimulation. Twenty patients with PD underwent MRI scanning. The PVS areas were visualized and segmented. Based on the size of the PVS areas, the patient group was split into 2 categories of large vs small PVSs. Probabilistic and deterministic tractography methods were applied to a diffusion-weighted data set. Fiber assignment was performed using motor cortex as an initiation seed and the globus pallidus interna and subthalamic nucleus, separately, as inclusion masks. Two exclusion masks used consisted of cerebral peduncles and the PVS mask. The center of gravity of the tract density map was measured and compared between the tracts generated with and without consideration of the PVS mask. The average differences between the center of gravity of the tracts made by excluding PVS and without excluding PVS using deterministic and probabilistic tractography methods were less than 1 mm. Statistical analysis showed nonsignificant differences between deterministic and probabilistic methods and differences between patients with large and small PVSs ( P > .05). This study demonstrated that the presence of enlarged PVS is unlikely to affect targeting of basal ganglia nuclei based on tractography.

Incomplete hippocampal inversion in patients with mutations in genes involved in sonic hedgehog signaling

Sonic hedgehog (Shh) signaling pathways are known to play an important role in the morphological development of the hippocampus in vivo, but their actual roles in humans have not been clarified. Hypothalamic hamartoma (HH) is known to be associated with germline or somatic gene mutations of Shh signaling. We hypothesized that patients with HH and mutations of Shh-related genes also show hippocampal maldevelopment and an abnormal hippocampal infolding angle (HIA). We analyzed 45 patients (age: 1–37 years) with HH who underwent stereotactic radiofrequency thermocoagulation and found Shh-related gene mutations in 20 patients. In addition, 44 pediatric patients without HH (age: 2–25 years) who underwent magnetic resonance imaging (MRI) examinations under the same conditions during the same period were included in this study as a control group. HIA evaluated on MRI was compared between patients with gene mutations and the control group. The median HIA at the cerebral peduncle slice in patients with the gene mutation was 74.36° on the left and 76.11° on the right, and these values were significantly smaller than the corresponding values in the control group (80.46° and 80.56°, respectively, p < 0.01). Thus, mutations of Shh-related genes were correlated to incomplete hippocampal inversion. The HIA, particularly at the cerebral peduncle slice, is a potential indicator of abnormalities of the Shh-signaling pathway.

Outcome in Stroke Patients is Associated with Age and Fractional Anisotropy in the Cerebral Peduncles : A Multivariate Regression Study

Outcome in Stroke Patients is Associated with Age and Fractional Anisotropy in the Cerebral Peduncles : A Multivariate Regression Study

Cavernous Malformations: What They Have Taught Us.

Cavernous Malformations: What They Have Taught Us.

Abstract Number ‐ 87: Successfull thrombectomy followed by balloon mount stent placement on acute basilar artery occlusion

Introduction Basilar artery occlusion accounts for 10% of all ischemic stroke caused by intracranial large vessel occlusion (LVO) with high morbidity and mortality. Endovascular intervention has been shown effective in the anterior circulation LVO but multiple trials, however a few trials failed to demonstrate the benefit of endovascular intervention over medical therapy, furthermore, there is no trial regarding the benefit of permanent stent deployment in the basilar artery over maximized medical therapy. Here we present a patient who presented with right side hemiplegia, facial droop, and dysmetria with National Institute of Health Stroke Scale of 19. CT head and neck angiography revealed acute basilar occlusion. Endovascular procedure was performed with successful thrombectomy utilizing stent retriever followed by placement of balloon mounted stent due to persistent critical basilar stenosis. Methods A case report Results MRI of the brain revealed acute ischemic stroke of bilateral cerebellar hemisphere, mid and left pons, left cerebral peduncles, and left thalamus. Repeat non‐contrast CT head revealed small bilateral thalamic hemorrhage but due to small size, dual antiplatelet therapy with aspirin and ticagrelor was initiated. After discharge, the patient developed upper extremity deep vein thrombosis for which apixaban was started. Despite dual antiplatelet therapy and anticoagulation, the patient continued to improve. Clinical follow‐up at 6 weeks the patient remained stable with mild residual weakness of the right extremities. Conclusions Thrombectomy with subsequent deployment of permanent stent can be considered as a safe and effective measure of basilar artery occlusion.

Long-Term Lower Limb Motor Function Correlates with Middle Cerebellar Peduncle Structural Integrity in Sub-Acute Stroke: A ROI-Based MRI Cohort Study

Crossed cerebellar diaschisis (CCD) has been widely investigated in patients with supratentorial stroke. However, the role of CCD in lower limb recovery after stroke is still unknown. In this study, using a region-of-interest-based analysis of diffusion tensor imaging (DTI), a total of 44 cases of stroke within 3 months onset were enrolled for assessment of the cerebral peduncle (CP) and middle cerebellar peduncles (MCP) in CCD. Compared with the control group, the fractional anisotropy ratio (rFA) and laterality index (LI) of the CP and MCP in the stroke group significantly decreased. The rFA of the MCP (unaffected side/affected side) showed a more significant correlation with 1-year paresis grading (PG), lower extremity PG, upper extremity PG, National Institutes of Health Stroke Scale (NIHSS), and functional independence measure (FIM) motor item score, in comparison to the rFA of the CP (affected side/unaffected side) (r = -0.698 vs. r = -0.541, r = -0.651 vs. r = -0.386, r = -0.642 vs. r = -0.565, r = -0.519 vs. r = -0.403, and r = 0.487 vs. r = 0.435, respectively). Furthermore, the LI of the CP had a more significant association with 1-year Brunel Balance Assessment (BBA), upper extremity PG, and Modified Rankin Scale (mRS) as compared to the LI of the MCP (r = 0.573 vs. r = 0.452; r = -0.554 vs. r = -0.528; and r = -0.494 vs. r = -0.344, respectively). We set the cutoff point for the MCP rFA at 0.925 (sensitivity: 79% and specificity: 100%) for predicting lower extremity motor function prognosis and found the receiver operating characteristic (ROC) curve of MCP rFA was larger than that of CP rFA (0.893 vs. 0.737). These results reveal that the MCP may play a significant role in the recovery of walking ability after stroke.

Reply to: Glioblastoma, IDH-Wildtype, CNS WHO Grade 4, Associated with Deep Brain Stimulation in a Patient with Essential Tremor: Report of a Case with Molecular Characterization and Review of the Literature.

We read with interest the letter from Burns et al1 regarding a case of glioblastoma associated with deep brain stimulation (DBS) in a patient with essential tremor. Their case adds another example of a high-grade brain tumor in close proximity to DBS electrodes. The nature of the association between DBS and malignancy remains unknown. The generally accepted incidence of high-grade glioma (HGG) is ~3.56/100,0002 in the United States. With more than 280,000 patients implanted with DBS worldwide,3 we could expect perhaps 10 DBS patients per year to be affected. To date, seven cases have been catalogued in the literature from 2010 to 2022,1 however, there may be more unreported cases. It remains unclear whether the rate of HGG is higher in patients with DBS. Thus far very few cases have been reported. A caveat is that most DBS are implanted for Parkinson's disease (PD),3 and if factors such as longer implantation and stimulation times were to increase the risk of HGG, then perhaps it takes many years longer than most PD patients live post-DBS to see malignancy develop. Hence, the observed incidence might not represent true risk in relation to DBS. The risk in subpopulations of DBS patients with longer duration implantation for dystonia, epilepsy, or neuropsychiatric indications may be higher. In our case, we highlight HGG in longer-term exposure of more than 20-years of DBS in a DYT-1 dystonia patient implanted at a younger age.4 Furthermore, the tumor centered in the cerebral peduncle, which is an uncommon location for spontaneous HGG. Although any associations remain theoretical, DBS is known to increase the expression of trophic factors and drive neurogenesis.5 With this in mind, DBS driving neoplasia would not be entirely surprising. Further studies will be needed to assess for a causal relationship such as by cataloguing tumor genotypes to understand if certain profiles are present in DBS-associated malignancy, as done by Burns et al.1 Additionally, understanding tumor location relative to the volume of tissue activated and not just the electrode location would be important in future studies. Even if DBS is implicated in increasing neoplasia, the risk is likely low given the low incidence seen to date. If the benefit of DBS therapy such as in refractory dystonia or tremor outweighs the low risks, then many clinicians and patients would likely still elect for DBS except in known cases of higher risk for brain malignancy, similar to other treatments like radiation therapy with risk of secondary malignancy decades later. In conclusion, the case presented by Burns et al1 is another important addition to the literature highlighting HGG in the context of DBS, and further highlights the need for more documentation of such cases and future studies investigating any association of DBS and chronic stimulation with brain malignancy. (1) Research Project: A. Conception, B. Organization, C. Execution; (2) Analysis: A. Design, B. Execution, C. Review and Critique; (3) Manuscript: A. Writing of the First Draft, B. Review and Critique. A.Balanchandar: 1C, 2A, 2B, 3A. A.Boutet: 1C, 2A, 2B, 3A, 3B. A.V.: 1C, 2C, 3B. J.G.: 1C, 2B. I.Y.M.C.: 1A, 2C, 3B. D.M.: 1A, 2C, 3B. R.P.M.: 1A, 2C, 3B. A.F.: 1A, 2C, 3B. S.K.K.: 1A, 1B, 2C, 3B. A.M.L.: 1A, 1B, 2C, 3B. Ethical Compliance Statement: We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this work is consistent with those guidelines. The authors confirm that the approval of an institutional review board was not required for this work. Informed consent was obtained for this case report. Funding Sources and Conflicts of Interest: No specific funding was received for this work. The authors declare that there are no conflicts of interest relevant to this work. Financial Disclosures for the Previous 12 Months: A.Balachandar, A.Boutet, A.V., J.G., I.Y.M.C., D.M., and R.P.M. report no funding sources in the past 12 months. A.M.L. and A.F. received honoraria and/or research support from Abbott, Insightec, Boston Scientific, and Medtronic. S.K.K. received grants/grants pending from the Canadian Institutes of Health Research, and received payment for lectures including service on speaker's bureaus from Medtronic.

Abstract 57: Sleep Duration Is Associated With Clinically Silent Brain Injury In Middle-aged Persons Without Stroke

Background: Evidence indicates that optimization of cardiovascular health during middle age leads to brain health benefits later in life. The AHA Life’s Simple 7, a research and public health construct capturing determinants of cardiovascular health, recently added sleep as a risk factor, becoming the Life’s Essential 8 (LE8). We hypothesize that suboptimal sleep duration worsens neuroimaging brain health profiles in middle-aged persons without stroke. Methods: We conducted a nested, cross-sectional neuroimaging analysis within the UK Biobank, a large population study conducted in the United Kingdom. We included participants without stroke/dementia who underwent a research brain MRI. We created a 6-category sleep score according to hours of sleep (best to worse): 7 to &lt;9h; 9 to &lt;10h; 6 to &lt;7h; 5 to &lt;6 or &gt;=10h; 4 to &lt;5h; and &lt;4h. We evaluated 3 neuroimaging traits: white matter hyperintensity volume (natural log-transformed), fractional anisotropy (FA) and mean diffusivity (MD). For the last two traits, we evaluated the first principal component of measurements obtained across 48 neuroanatomical regions. Results: Of 502,408 participants enrolled in the UKB, 39,937 (7.9%) stroke/dementia-free enrollees participated in the brain MRI study (mean age 55, 53% female). The distribution of sleep categories was: 1 (n=28,958, 72.51%), 2 (n=2060, 5.16%), 3 (n=7165, 17.94%), 4 (n=1,562, 3.91%), 5 (n=163, 0.41%) and 6 (n=29, 0.07%). In multivariable linear regression analyses, a higher (worse) sleep score was associated with larger WMH volume (beta 0.026, SE=0.0046; p&lt;0.001) and worse FA profile (beta 0.003, SE=0.0008; p&lt;0.001), with no association observed for MD (p=0.77). For FA, when evaluating the 48 neuroanatomical regions separately, the most compromised areas were the right cerebral peduncle (p&lt;0.001) and left and right cerebellar peduncles (p&lt;0.001). Conclusion: Among middle-aged participants enrolled in the UKB, suboptimal sleep duration was significantly associated with adverse neuroimaging brain health profiles. These results emphasize the importance of sleep duration, the new component of the LE8, in determining brain health in middle-aged persons who have not developed clinically evident manifestations of poor brain health (stroke).

Secondary dystonia following parenchymal brain tumors

BackgroundSecondary dystonia has been associated with diverse etiologies. Dystonia associated with brain tumors has not been well characterized. ObjectivesTo characterize dystonia and relationship with parenchymal brain tumors. MethodsWe present six patients (1.03%) with dystonia related to parenchymal brain tumors, among 580 screened cases. ResultsContralateral hemidystonia was observed in four cases, followed by focal limb (n = 1) and cervical dystonia (n = 1). Dystonia presented during the phase of tumor growth in four cases, and following tumor treatment in two, one case had re-emergent dystonia. Tumors were low-grade (WHO I or II) and located in the basal ganglia (n = 3), cortical areas (n = 2), thalamus (n = 1) and cerebral peduncle (n = 1). ConclusionsSecondary dystonia may be caused by brain tumors in diverse locations including basal ganglia, cortex and thalamus. It may be the presenting symptom of brain tumor or follow surgical resection combined with ancillary therapy.

The role of magnetic resonance imaging in the early diagnosis of chronic lymphocytic inflammation (CLIPPERS syndrome)

Background: Chronic lymphocytic inflammation with perivascular contrast enhancement in the pons responsive to steroids (CLIPPERS) is a rare and relatively new pathology and magnetic resonance imaging (MRI) is highly important in its diagnosis.&#x0D; Clinical case description: The analysis of the MRI results revealed typical changes characteristic of CLIPPERS, such as contrast-positive small-point and curvilinear lesions of the pons, medulla oblongata and midbrain, as well as of the cerebral peduncles and cerebellum. In addition to the changes we described, according to the literature, lesions of the white matter of the large hemispheres and thalami may also be observed in the syndrome of chronic lymphocytic inflammation.&#x0D; Conclusion: MRI not only enables one to achieve high-quality neuroimaging of CLIPPERS, but also allows avoiding invasive, traumatic diagnostic methods.