Linking Type and Extent of Head Trauma to Cavum Septum Pellucidum in Older Adults With and Without Alzheimer Disease and Related Dementias.

BACKGROUND AND OBJECTIVES: Cavum septum pellucidum (CSP) is a common but nonspecific MRI finding in individuals with prior head trauma. The type and extent of head trauma related to CSP, CSP features specific to head trauma, and the impact of brain atrophy on CSP are unknown. We evaluated CSP cross-sectionally and longitudinally in healthy and clinically impaired older adults who underwent detailed lifetime head trauma characterization. METHODS: This is an observational cohort study of University of California, San Francisco Memory and Aging Center participants (healthy controls [HCs], those with Alzheimer disease or related dementias [ADRDs], subset with traumatic encephalopathy syndrome [TES]). We characterized traumatic brain injury (TBI) and repetitive head impacts (RHI) through contact/collision sports. Study groups were no RHI/TBI, prior TBI only, prior RHI only, and prior RHI + TBI. We additionally looked within TBI (1, 2, or 3+) and RHI (1-4, 5-10, and 11+ years). All underwent baseline MRI, and 67% completed a second MRI (median follow-up = 5.4 years). CSP measures included grade (0-4) and length (millimeters). Groups were compared on likelihood of CSP (logistic regression, odds ratios [ORs]) and whether CSP length discriminated groups (area under the curve [AUC]). RESULTS: Our sample included 266 participants (N = 160 HCs, N = 106 with ADRD or TES; age 66.8 ± 8.2 years, 45.3% female). Overall, 123 (49.8%) participants had no RHI/TBI, 52 (21.1%) had TBI only, 41 (16.6%) had RHI only, 31 (12.6%) had RHI + TBI, and 20 were classified as those with TES (7.5%). Compared with no RHI/TBI, RHI + TBI (OR 3.11 [1.23-7.88]) and TES (OR 11.6 [2.46-54.8]) had greater odds of CSP. Approximately 5-10 years (OR 2.96 [1.13-7.77]) and 11+ years of RHI (OR 3.14 [1.06-9.31]) had higher odds of CSP. CSP length modestly discriminated participants with 5-10 years (AUC 0.63 [0.51-0.75]) and 11+ years of prior RHI (AUC 0.69 [0.55-0.84]) from no RHI/TBI (cut point = 6 mm). Strongest effects were noted in analyses of American football participation. Longitudinally, CSP grade was unchanged in 165 (91.7%), and length was unchanged in 171 (95.5%) participants. DISCUSSION: Among older adults with and without neurodegenerative disease, risk of CSP is driven more by duration (years) of RHI, especially American football, than number of TBI. CSP length (≥6 mm) is relatively specific to individuals who have had substantial prior RHI. Neurodegenerative disease and progressive atrophy do not clearly influence development or worsening of CSP.

C9orf72 Repeat Expansion Initially Presenting as Late-Onset Bipolar Disorder With Psychosis.

INTRODUCTION: C9orf72 expansion is the most common genetic abnormality in behavioral variant frontotemporal dementia (bvFTD) and amyotrophic lateral sclerosis. Although psychiatric prodromes are common in C9orf72 expansion carriers, there are only scattered reported cases of primary psychiatric disorders, such as bipolar disorder, diagnosed at disease onset. Moreover, C9orf72 carrier status is rarely identified in bipolar disorder genetic studies. CASE REPORT: A 51-year-old, right-handed woman with 16 years of education presented for evaluation of long-standing cognitive and behavioral change. She initially displayed symptoms of mania and florid, multimodal psychotic symptoms at age 39. Her bipolar disorder symptoms were initially responsive to medication; however, she later developed executive dysfunction and behavioral symptoms consistent with bvFTD. She became progressively nonverbal, and her limited speech was notable for speech apraxia. At the time of presentation, she demonstrated cortical sensory deficit, ideomotor and oral-buccal apraxia, and unstable gait. Neuroimaging revealed diffuse brain atrophy. Postmortem histopathological evaluation revealed frontotemporal lobar degeneration with TDP-43 inclusions, type B, and genetic study identified C9orf72 expansion. A detailed review of family history found a strong paternal history of bipolar disorder and substance use disorder. CONCLUSIONS: We describe a rare case of C9orf72 expansion initially characterized by late-onset bipolar disorder and florid, multimodal psychotic symptoms, followed years later by bvFTD diagnosis. This report emphasizes the importance of completing a neurological examination, obtaining a detailed family history, and pursuing genetic screening to distinguish between primary psychiatric disorder and bvFTD in individuals who meet the criteria for late-onset bipolar disorder.

Anti-Amyloid Immunotherapies for Alzheimer's Disease: A 2023 Clinical Update.

The amyloid cascade hypothesis is a useful framework for therapeutic development in Alzheimer's disease (AD). Amyloid b1-42 (Aß) has been the main target of experimental therapies, based on evidence of the neurotoxic effects of Aß, and of the potential adverse effects of brain Aß burden detected in humans in vivo by positron emission tomography (PET). Progress on passive anti-amyloid immunotherapy research includes identification of antibodies that facilitate microglial activation, catalytical disaggregation, and increased flow of Aß from cerebrospinal fluid (CSF) to plasma, thus decreasing the neurotoxic effects of Aß. Recently completed phase 2 and 3 trials of 3rd generation anti-amyloid immunotherapies are supportive of their clinical efficacy in reducing brain Aß burden and preventing cognitive decline. Data from recent trials implicate these agents as the first effective disease-modifying therapies against AD and has led to the US Food and Drug Administration (FDA) recent approval of aducanumab and lecanemab, under an accelerated approval pathway. The clinical effects of these agents are modest, however, and associated with amyloid-related imaging abnormalities (ARIA). Testing the effects of anti-Aß immunotherapies in pre-symptomatic populations and identification of more potent and safer agents is the scope of ongoing and future research. Innovations in clinical trial design will be the key for the efficient and equitable development of novel anti-Aß immunotherapies. The progress in the field of AD therapeutics will bring new clinical, logistical, and ethical challenges, which pose to revolutionize the practice of neurology, dementia care, and preventive cognitive healthcare.

Response patterns for individuals receiving contingent skin shock aversion intervention to treat violent self-injurious and assaultive behaviours.

A small proportion of patients with intellectual disabilities (IDs) and/or autism spectrum disorder (ASD) exhibit extraordinarily dangerous self-injurious and assaultive behaviours that persist despite long-term multidisciplinary interventions. These uncontrolled behaviours result in physical and emotional trauma to the patients, care providers and family members. A graduated electronic decelerator (GED) is an aversive therapy device that has been shown to reduce the frequency of severe problem behaviours by 97%. Within a cohort of 173 patients, we have identified the four most common patterns of response: (1) on removal of GED, behaviours immediately return, and GED is reinstated; (2) GED is removed for periods of time (faded) and reinstated if and when behaviours return; (3) a low frequency of GED applications maintains very low rates of problem behaviours; and (4) GED is removed permanently after cessation of problem behaviours. GED is intended as a therapeutic option only for violent, treatment-resistant patients with ID and ASD.

Neuro-Behcet's disease: An update on diagnosis, differential diagnoses, and treatment.

Neuro-Behcet's disease (NBD) is defined as a combination of neurologic symptoms and/or signs in a patient with Behcet's disease (BD). Relevant syndromes include brainstem syndrome, multiple-sclerosis like presentations, movement disorders, meningoencephalitic syndrome, myelopathic syndrome, cerebral venous sinus thrombosis (CVST), and intracranial hypertension. Central nervous involvement falls into parenchymal and non-parenchymal subtypes. The parenchymal type is more prevalent and presents as brainstem, hemispheric, spinal, and meningoencephalitic manifestations. Non-parenchymal type includes CVST and arterial involvement. Perivascular infiltration of polymorphonuclear and mononuclear cells is seen in most histo-pathologic reports. In parenchymal NBD, cerebrospinal fluid (CSF) generally exhibits pleocytosis, increased protein and normal glucose. In NBD and CVST, CSF pressure is increased but content is usually normal. The typical acute NBD lesions in brain magnetic resonance imaging (MRI) are mesodiencephalic lesions. The pattern of extension from thalamus to midbrain provides a cascade sign. Brain MRI in chronic NBD usually shows brain or brainstem atrophy and/or black holes. The spinal MRI in the acute or subacute myelopathies reveals noncontiguous multifocal lesions mostly in cervical and thoracic lesions. In chronic patients, cord atrophy can also be seen. Brain MRI (particularly susceptibility-weighted images), MR venography (MRV) and computerized tomographic venography (CTV) can be used to diagnose CVST. Parenchymal NBD attacks can be treated with glucocorticoids alone or in combination with azathioprine. For patients with relapsing-remitting or progressive courses, shifting to more potent immunosuppressive drugs such as mycophenolate, methotrexate, cyclophosphamide, or targeted therapy is warranted. For NBD and CVST, immunosuppressive drugs with or without anticoagulation are suggested.

Clinical Outcomes of Posterolateral Fusion vs. Posterior Lumbar Interbody Fusion in Patients with Lumbar Spinal Stenosis and Degenerative Instability.

BACKGROUND: Degenerative lumbar spine disease can lead to lumbar spine instability. Lumbar spine instability is defined as an abnormal response to applied loads characterized kinematically by abnormal movement in the motion segment beyond normal constraints. Patients with lumbar spinal stenosis (LSS) typically present with low back pain (LBP), cramping, cauda equine syndrome, and signs of nerve root compression associated by weakness, numbness and tingling in their legs that are worsened with standing and walking. This degenerative condition severely restricts function, walking ability, and quality of life (QOL). OBJECTIVES: This study aims to compare clinical and radiological outcomes of posterolateral fusion (PLF) with posterior lumbar interbody fusion (PLIF) with posterior instrumentation in the treatment of LSS and degenerative instability. STUDY DESIGN: A randomized prospective controlled clinical study. METHODS: In this prospective study, 88 patients with LSS and degenerative instability were randomly allocated to one of 2 groups: PLF (Group I) or PLIF (Group II). Primary outcomes were the control of LBP and radicular pain, evaluated with visual analog scale (VAS), the improvement of QOL assessed by the Oswestry disability index (ODI) scale, and measurement of fusion rate, Cobb angle, spinal sagittal balance, and modic changes in the 2 groups. RESULTS: At 24 months postoperatively, the mean reduction in VAS scores in Group I was more than in Group II (5.67 vs. 5.48, respectively) and the patients in Group I had more improvement in the ODI score than the patients in Group II (42.75 vs. 40.94, respectively). There was a statistically significant difference between the preoperative and postoperative sagittal balance in the 2 groups. The mean Cobb angle changed significantly in the 2 groups. LIMITATIONS: There are few prospective studies of PLIF or PLF in patients with LSS and degenerative lumbar spine instability, and a limited number of studies which exists have examined the safety and outcome of each procedure without comparing it with other fusion techniques. Because most of the studies in the literature have been conducted in the patients with IS, we could not compare and contrast our findings with studies in patients with LSS and degenerative lumbar spine instability. In addition, although in our study the findings at a 24-month follow-up period showed that PLF was better than PLIF in these patients, there were some studies in which the authors reported that PLIF showed better clinical results than PLF at a 48-month follow-up period. So we suggest that rigorous controlled trials at longer follow-up periods should be undertaken in groups of patients with LSS and degenerative lumbar spine instability who undergo posterior decompression and instrumented fusion to help to determine the ultimate best fusion technique for these patients. CONCLUSION: PLF with posterior instrumentation provides better clinical outcomes and improvement in the LBP, radicular pain, and functional QOL, more correction of the Cobb angle, more restoration of sagittal alignment, more decrease in Modic type 1, and more increase in Modic type 0, despite the low fusion rate compared to PLIF. KEY WORDS: Lumbar spinal stenosis, degenerative instability, posterolateral fusion, posterior lumbar interbody fusion, low back pain, quality of life, cobb angle, fusion rate, modic changes, sagittal balance.

Discrepancies in stereotaxic coordinate publications and improving precision using an animal-specific atlas.

Rodent brain atlases have traditionally been used to identify brain structures in three-dimensional space for a variety of stereotaxic procedures. As neuroscience becomes increasingly sophisticated, higher levels of precision and consistency are needed. Observations of various atlases currently in use across labs reveal numerous coordinate discrepancies. Here we provide examples of inconsistencies by comparing the coordinates of the boundaries of various brain structures across six atlas publications. We conclude that the coordinates determined by any particular atlas should be considered as only a first approximation of the actual target coordinates for the experimental animal for a particular study. Furthermore, the coordinates determined by one research team cannot be assumed to be universally applicable and accurate in other experimental settings. To optimize precision, we describe a simple protocol for the construction of a customized atlas that is specific to the surgical approach and to the species, gender, and age of the animal used in any given study.

Administration of electroconvulsive therapy for depression associated with deep brain stimulation in a patient with post-traumatic Parkinson's Disease: a case study.

BACKGROUND: Deep brain stimulation (DBS) has been shown to be effective for parkinsonian symptoms poorly responsive to medications. DBS is typically well-tolerated, as are the maintenance battery changes. Here we describe an adverse event during a battery replacement procedure that caused rapid onset of severe depression. CASE PRESENTATION: The patient is a 58-year-old woman who was in a serious motor vehicle accident and sustained a concussion with loss of consciousness. Within weeks of the accident she began developing parkinsonian symptoms that progressively worsened over the subsequent 10 years. Responding poorly to medications, she received DBS, which controlled her movement symptoms. Five years after initiating DBS, during a routine battery change, an apparent electrical event occurred that triggered the rapid onset of severe depression. Anti-seizure and antidepressant medications were ineffective, and the patient was offered a course of electroconvulsive therapy (ECT), which resulted in complete reversal of her depressive episode. CONCLUSION: Parkinson's syndrome can be seen after a single closed head injury event. Post-traumatic parkinsonism is responsive to DBS; however, DBS has been associated with an infrequent occurrence of dramatic disruption in mood. ECT is a therapeutic option for patients who develop intractable depressive illness associated with DBS.

Cranioplasty Results after Application of Anti-adhesive Films (OrthoWrap™) in Traumatic Decompressive Craniectomy.

OBJECTIVE: To determine the effects of application of anti-adhesive films (OrthoWrap™) in traumatic decompressive craniectomy on prevention of adhesion formation and facilitation of subsequent cranioplasty. METHODS: This was a retrospective cohort study being performed in ShahidRajaei hospital (Shiraz Level I trauma center) during a 12-month period (from March 2012 to April 2013) including 93 patients undergoing traumatic decompressivecraniectomy.Patients who received OrthoWrap™ during the initial craniectomy (n=44) were compared to those who did not (n=49). Two study groups were matched regarding the baseline characteristics. The perioperative indices including the surgical time, amount of bleeding, transfusion and 6-month Glasgow Outcome Scale (GOS) were compared between two study groups. RESULTS: There was no significant difference between two study groups regarding the baseline characteristics. We found that the cranioplasty duration (113.3±33.2 vs. 146.9±34.9 minutes; p<0.001) and amount of intraoperative bleeding (182.1±98.3 vs. 270.6±77.6 mL; p=0.043) was significantly lower in those who had OrthoWrap™ compared to control group. The final GCS (p=0.052) as well as GOSE (p=0.653) was comparable between groups. The infection rate was comparable between two study groups (p=0.263). CONCLUSION: Application of OrthoWrap™ during decompressive craniectomy in those with severe traumatic brain injury is associated with shorter duration of operation and less intraoperative bleeding in subsequent cranioplasty. Infection rate and neurologic outcome was comparable between study groups.

Flow Augmentation in Acute Ischemic Stroke.

There is an urgent need for additional therapeutic options for acute ischemic stroke considering the major pitfalls of the options available. Herein, we briefly review the role of cerebral blood flow, collaterals, vasoreactivity, and reperfusion injury in acute ischemic stroke. Then, we reviewed pharmacological and interventional measures such as volume expansion and induced hypertension, intra-aortic balloon counterpulsation, partial aortic occlusion, extracranial-intracranial carotid bypass surgery, sphenopalatine ganglion stimulation, and transcranial laser therapy with regard to their effects on flow augmentation and neuroprotection.

Tinnitus 3 years after strangulation.

Because psychogenic tinnitus can be a presentation of a wide range of psychiatric diseases such as anxiety disorders, somatoform and mood disorders, and personality disorders, the presence of tinnitus in the patient in this case can be easily misdiagnosed as her coexisting major depressive disorder. If brain imaging had been the only modality used, this case patient's cervical dissecting pseudoaneurysm would have been overlooked. Examination of carotid pulses and detection of carotid bruits were crucial parts in the diagnosis of the current patient's pseudoaneurysm.

Diagnostic Accuracy of Peripheral White Blood Cell Count, Fever and Acute Leukocutosis for Bacterial Meningitis in Patients with Severe Traumatic Brain Injury.

OBJECTIVE: To determine the diagnostic value of serum white blood cell (WBC) count, fever (>38˚C) and WBC rise (>10%) for bacterial meningitis in patients with severe traumatic brain injury (TBI). METHOD: This cross-sectional study was conducted in Shahid Rajaei hospital affiliated with Shiraz University of Medical Sciences during a 1-year period from 2013 to 2014. We included consecutively all the patients with severe TBI admitted to our center during the study period who were febrile (>38˚C orally) and underwent lumbar puncture (LP) and analysis and culture of cerebrospinal fluid (CSF). Laboratory analysis of CSF and blood were performed within 2 hours of LP. CSF culture was considered the gold standard for diagnosis of bacterial meningitis. The sensitivity, specificity, positive and negative predictive value (PPV, NPV) of peripheral blood WBC count, fever (>38˚C) and WBC rise (>10%) was determined according to the CSF culture. RESULTS: Overall we included242 consecutive patients with severe TBI. The mean age of the participants was 32.8 ± 17.4 years. Acinetobacter was the most common organism found in the CSF cultures. The sensitivity and specificity of peripheral WBC count (>10,000)was 48.4% (95% CI: 0.42-0.56) and 47% (95% CI: 0.37-0.58) respectively. The PPV and NPV was 13.1% (95% CI: 0.33-0.52) and 84.8% (95% CI: 0.42-0.61), respectively. The AUC for WBC count was 0.478 (95% CI: 0.37-0.58) indicating low accuracy for the diagnosis of bacterial meningitis. The AUC for WBC rise (>10%) and temperature >38˚C was0.460 (95% CI: 0.351-0.569) and 0.517 (95% CI: 0.410-0.624) respectively, both indicating low accuracy for diagnosis of bacterial meningitis. CONCLUSION: The results of the current study indicates that peripheral blood leukocyte count, fever (>38˚C) and WBC rise (>10%) is a non-reliable marker for diagnosis of bacterial meningitis in patients with severe TBI.

Comparison of the health-related quality of life between epileptic patients with partial and generalized seizure.

BACKGROUND: Epilepsy is defined as recurrent unprovoked febrile seizures, which cause disability in patients. This study aims to assess the health-related quality-of-life (QOL) in epileptic patients in Fars Province, southern Iran. METHODS: One-hundred epileptic patients, above 18 years, referred to Shiraz University of Medical Sciences affiliated clinics, were included. The QOL of patients with generalized and partial seizure were assessed using the Iranian valid and reliable Sf-36 questionnaire. Patients' socio-demographic and their disease features were also compared with each other using a questionnaire. RESULTS: In partial epilepsy group (n = 24), the married patients in social functioning (SF) aspect of QOL (64.42 ± 14.29) (P = 0.024), the patients on antiepileptic drugs (AEDs) monotherapy in both physical functioning (PF) (88.75 ± 11.57) (P = 0.030) and SF (75.00 ± 6.68) (P = 0.022) aspects, the employed patients in PF aspect of QOL (P = 0.023) (91.87 ± 8.83) and those with high income in mental health aspect of QOL (P = 0.036 and correlation coefficient = 0.413) got better scores compared with the partial epileptic patients who were single, on polytherapy, unemployed and had low to moderate income. In generalized epilepsy group (n = 76), patients on AEDs monotherapy in PF aspect of QOL (P = 0.025) (78.33 ± 24.36) and employed patients in vitality aspect (P = 0.023) (57.00 ± 28.25) had better scores. Data were analyzed using SPSS for windows. CONCLUSION: Epilepsy can affect patient's life in a number of ways such as their lives, marriage, occupation, and education. We can encourage patients to find a partner, continue higher education and try to find a job.