Progressive Behavioral Changes Research Articles

GABA-A Receptor Meningoencephalitis presenting with New Onset Refractory Status Epilepticus and Reversible Vasculopathy (P4-5.002)

<h3>Objective:</h3> Discuss current clinical and neuroimaging phenotypes associated with GABA-A receptor encephalitis as applied to the case of a 14-year old female with a two-month history of behavior change and subsequent development of new onset refractory status epilpeticus and reversible vasculopathy. <h3>Background:</h3> Anti-Gamma Amino Butyric Acid-A (GABA-A) Receptor Encephalitis is an antibody mediated encephalitis which manifests with neurocognitive dysfunction, pharmacoresistant seizures, movement disorders, dysautonomia, and multifocal T2 FLAIR lesions in the cortex and subcortex without mass effect or enhancement. Not all patients fulfill these characteristics, creating challenges in early identification and treatment. <h3>Design/Methods:</h3> n/a <h3>Results:</h3> In this case we will discuss the current clinical and neuroimaging phenotypes associated with GABA-A receptor encephalitis cited in the literature and challenge their application to the case of a 14-year old female with a two-month history of behavior change and weight loss who was found to have serum and CSF positive anti-GABA-A receptor α1 subunit encephalitis. MRI showed persistent multifocal cortical/subcortical T2 changes during evaluation. Clinical course progressed from her initial behavioral changes to development of dysautonomia, new onset refractory status epilepticus (NORSE), and reversible vasculopathy. NORSE did not resolve until immunotherapy was escalated to apharesis and rituximab. Patient clinically improved and started cyclophosphamide for maintenance immunotherapy. <h3>Conclusions:</h3> GABA-A Receptor Encephalitis clinical features demonstrate progressive behavioral changes, dysautonomia, and new onset refractory status epilepticus. Radiographic features include persistent multifocal cortical/subcortical T2 changes. This case reinforces the previously described clinical and radiographic phenotypes of GABA-A receptor encephalitis, as well as the role of timely escalation of immunotherapy treatment. Further investigation is needed to observe the impact of primary immunodeficiency disorders and antibody mediated encephalitis disease. <b>Disclosure:</b> Dr. Garcia has nothing to disclose. Dr. Crowson has nothing to disclose. Dr. Angappan has nothing to disclose. Dr. Chen has received research support from OHSU Foundation. Dr. Yadav has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen Pharmaceuticals. Dr. Yadav has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bristol Myers Squibb Foundation. Dr. Yadav has received personal compensation in the range of $500-$4,999 for serving as a Consultant for EMD-Serono . The institution of Dr. Yadav has received research support from Department of Veterans Affairs. Dr. Yadav has received research support from NIH. Dr. Yadav has received research support from PCORI. Dr. Yadav has received research support from NMSS. The institution of Dr. Yadav has received research support from Department of Veterans Affairs. The institution of Dr. Yadav has received research support from Tykeson Family Foundation Endowed Professorship.

Atypical imaging and clinical presentation of fulminant subacute sclerosing panencephalitis

Subacute sclerosing panencephalitis (SSPE) is a late progressive fatal central nervous system sequelae of measles infection. The diagnosis is made based on clinical and electroencephalography (EEG) findings and confirmed by elevated titers of anti-measles antibodies in cerebrospinal fluid. The usual clinical presentation is in the form of progressive behavioral change, cognitive decline, and myoclonic jerks with some cases presenting in an atypical manner in the form of ataxia, epilepsy, and stroke. EEG is quiet characteristic in the form of periodic discharges of slow wave complex. Magnetic resonance imaging (MRI) early in the disease is usually normal with abnormal scans showing focal leukodystrophy, predominantly in the posterior cerebral white matter, and development of cortical atrophy with disease progression. Cord involvement is not common in SSPE. We report a child with SSPE who had initial presentation with cerebellar ataxia, acute progression of encephalitis, and atypical EEG findings. MRI brain on the initial presentation showed very subtle and focal abnormality which later progressed to have disseminated brain lesions and dorsal cord myelitis and further in the disease course showed cerebral venous sinus thrombosis. This case report emphasizes that SSPE can have very atypical presentation with rapid deterioration and can mimic as acute encephalitis or demyelinating disease.

Developmental Autonomous Behavior: An Ethological Perspective to Understanding Machines

Developmental autonomous behavior refers to the general ability of a machine to acquire new skills and behavior from its birth to maturity on its own without human intervention. This article describes the principles of behavior development in machines, providing a practical framework to analyze and synthesize machines with developmental capabilities. Inspired by biological views of behavioral causation, the work emphasizes principled explanations to, not only the “how” question on mechanisms but also the “why” question on causation of behavior development. This ethology-oriented perspective offers a renewed opportunity to construct a theoretical framework from the ground up, overcoming the age-old problems of intrinsic motivation and symbol emergence in autonomous machines. One of the key contributions of this article is the logical explanation of why and how value systems drive successive development of memory functions, resulting in progressive changes in behavior from innate reflexive to episodic, procedural, and autonomic behavior. Another notable contribution is the logical and plausible explanation of why and how a physical sensorimotor system evolves to manipulate its internal memory, fostering conceptual and social behavior development. This article provides an extensive review of prior research, followed by detailed descriptions of the causality and mechanisms of behavior development, and concludes with discussions on criticism, future work, ethics, and system architecture.

Implications of lifestyle medicine in medical practice.

Globally, we are seeing a rise in non-communicable diseases such as obesity, hypertension, diabetes, metabolic syndrome, chronic respiratory diseases, cancer, etc., due to stressful lifestyle in this competitive world. Most of the non-communicable diseases are associated with lifestyle behavior. Presently, the role of lifestyle medicine is very critical and important in the management of chronic lifestyle-associated disorders. Considering the above facts, we decided to review the literature to gain a deeper insight into the implications of lifestyle medicine in medical practice. A literature search was conducted on PubMed, Scopus and Google Scholar databases. We observed that lifestyle medicine intervention is a growing and newer discipline and is being employed along with conventional management of non-communicable diseases by medical practitioners today, as they are strongly associated with lifestyle behaviors and practices. Motivation for change in lifestyle is challenging because it depends on the patient's determination and eagerness to adapt and accommodate to the newer lifestyle pattern. The medical practitioners should spend time in coaching patients on lifestyle-related health education. Guidance and coaching by medical practitioners will help patients adapt to practices of maintaining regular physical activity, a balanced diet, good sleep hygiene, and avoid addictions of tobacco and alcohol as part of life. Introducing real and progressive evidence-based behavioral changes to reduce the risks of lifestyle-related acute and chronic diseases in medical practice will reduce the burden of non-communicable disease.

HEALTH COACHING FOR DEMENTIA CAREGIVERS: LESSONS LEARNED FROM THE ICARE4ME STUDY

Abstract Frontotemporal dementia (FTD) is a common cause of young-onset neurodegenerative disease that causes progressive changes in behavior and personality. FTD is often diagnosed around age 60, creating complex care needs that result in caregivers of persons with FTD experiencing high rates of depression, burden, and poor self-care. The iCare4Me for FTD study (NCT04686266) randomized 15 caregivers to receive a virtual health coaching intervention over 6 months (10 sessions) and 15 caregivers to the control group. To better understand the caregivers’ experience with the health coach intervention, two focus groups with intervention group caregivers (n=5) were held. Focus groups were recorded, transcribed and coded using content analysis. Caregivers reported the most valuable aspect was the relationship that was developed with their health coach. Caregivers particularly valued having someone to talk to who was outside their immediate social and support networks. It was noted the structured self-care curriculum served as a good backbone for discussions, but more specific coping conversations related to loss of patient empathy, prognostic uncertainty, and anticipatory grief are needed. One caregiver described being, “… awash in grief and it's affected my memory” while another described “grief is a big issue and I don't really find too many people understand it, because my husband is alive, but so many parts of him are gone”. These findings will be used to inform future studies utilizing health coaches for caregivers of persons with FTD. Implications for evidence-based virtual health coaching interventions with caregivers of persons living with FTD will be described.

Salidroside Alleviates Diabetic Cognitive Dysfunction Via B3galt2/F3/Contactin Signaling Pathway in Mice

Diabetes is frequently accompanied by cognitive impairment with insidious onset, and progressive cognitive and behavioral changes. β-1, 3-galactosyltransferase 2 (B3galt2) contributes to glycosylation, showing a clue for neuronal apoptosis, proliferation and differentiation. However, the role of B3galt2 in diabetic cognitive dysfunction (DCD) has not been investigated. In the present study, we aimed to explore the role of B3galt2 in DCD. Additionally, the potential therapeutic effects of salidroside on DCD was also explored. Diabetic C57BL/6J mice showed cognitive dysfunction together with down-regulated B3galt2. Overexpression of B3galt2 reversed the cognitive decline of diabetic C57BL/6J. Moreover, cognitive impairment was aggravated in B3galt2+/− diabetic mice compared with C57BL/6J diabetic mice. Immunohistochemistry fluorescence indicated that B3galt2 and F3/Contactin were co-localized in the hippocampal regions. Importantly, the expression of F3/Contactin can be regulated by the manipulation of B3galt2, overexpression of which assuaged hippocampal neuronal damage, protected the synapsin, and reduced neuronal apoptosis in diabetic mice. Interestingly, SAL alleviated DCD and reversed the expression of B3galt2 in diabetic C57BL/6J mice. These findings indicate that inhibition of B3galt2/F3/Contactin pathway contributes to DCD, and participates in SAL reversed DCD.

Progranulin upregulation by antisense oligonucleotides targeting regRNAs for treatment of FTD‐GRN

AbstractBackgroundHeterozygous mutations in progranulin (GRN) gene leading to progranulin protein (PGRN) haploinsufficieny are the major genetic cause of GRN‐related frontotemporal dementia (FTD‐GRN)1, 2 and 3. Decreased levels of PGRN disrupt lysosome homeostasis, cause aberrant microglia activation and neuronal cell death resulting in progressive behavioral changes, language deficits and memory impairment4. We hypothesize that upregulation of PGRN in both neuronal cells and microglia would be effective for treating FTD‐GRN patients.MethodRegulatory RNAs (regRNAs) are a class of noncoding RNAs that modulate gene transcription. We have developed an RNA Actuating Platform (RAPTM) that identified regRNAs and enables tunable upregulation of genes by specific targeting of regRNAs with antisense oligonucleotides (ASOs).ResultOur platform identified shared GRN regRNAs in human iPSC‐derived neuron and microglia like cells (iMGLs). ASOs targeting shared regRNAs were screened in a human neuroblastoma cell line to identify lead ASOs that upregulate GRN at least 2‐fold. We showed that the lead ASOs upregulate GRN in both human iPSC‐derived neurons and iMGL cells. Moreover, this level of GRN upregulation was sufficient to rescue staurosporine‐induced toxicity in FTD‐GRN patient iPSC‐derived neurons.Furthermore, we identified mouse Grn regRNA‐targeting ASOs that upregulate Grn transcription 2.5‐fold in mouse neuroblastoma cell lines and primary neurons. We tested these ASOs for efficacy in an FTD‐GRN mouse model (Grn+/tm1.1Far )5 by intracerebroventricular injection. Grn upregulation is observed across disease‐relevant brain regions, including cortex in the Grn haploinsufficient mice.ConclusionHere, we describe the development of oligonucleotide drug candidates that target regRNAs to upregulate GRN expression as a therapeutic approach for FTD‐GRN. We believe that our strategy will restore secreted and lysosomal PGRN levels in both microglia and neurons thereby decreasing neuroinflammation and neurotoxicity. We are developing these oligonucleotides as a disease modifying treatment for patients with FTD‐GRN.

Chronicling the diagnostic journey, symptom experiences, and disease impact in frontotemporal degeneration

AbstractBackgroundFrontotemporal degeneration (FTD) is an umbrella term encompassing a range of rare neurodegenerative disorders that cause progressive decline or changes in cognition, language, behavior, and personality. The FTD Insights Survey was created with the aim of gathering information on the lived experience of FTD. Here we present a subset of survey data chronicling the diagnostic journey, symptoms experienced, and the impact of FTD on distress, quality of life, and independence, in the mild to moderate stages of the disease course.MethodIn total, 1,796 individuals completed the survey. Persons reported as severe to profoundly impaired due to FTD, as well as past caregivers, were excluded for this analysis. The resulting cohort included 219 individuals diagnosed with FTD and 437 current care partners, representing a range of FTD diagnoses (n = 395 behavioral variant frontotemporal dementia or Pick’s disease; n = 155 primary progressive aphasia; n = 61 progressive supranuclear palsy or corticobasal syndrome; n = 13 FTD with amyotrophic lateral sclerosis; n = 32 unknown).ResultAround half of survey respondents saw three or more doctors before an FTD diagnosis was given, and a range of prior diagnoses, including primary psychiatric disorders, Parkinson’s disease, or Alzheimer’s disease, were noted. Most frequently endorsed symptoms tended to be consistent with clinical characteristics of the specific diagnosis, though there was significant variability in symptoms reported within diagnostic categories as well as considerable overlap in symptoms between diagnostic categories. Cognitive and language symptoms of FTD were generally most distressing to the person diagnosed, and a loss of independence was highly endorsed as affecting quality of life. The distinct perspectives of diagnosed persons and care partners regarding disease impact differed notably for bvFTD/Pick’s disease. Participating independently in activities, within the home, outside the home, and with other people, were reported as challenging for people living with FTD, underscoring the significant disruption to daily living even at the mild and moderate stages of disease.ConclusionOverall, by heeding the perspectives of those living with FTD, we can begin to design more meaningful research studies, provide better care, and develop new therapies that improve quality of life

2022 ASSBI PRESIDENTIAL ADDRESS. Reflections on language and primary progressive aphasias

AbstractPrimary progressive aphasias are rare younger-onset dementias. As the label denotes, these dementias are characterised clinically by marked changes in language skills. Evidence over the years has shown that individuals with primary progressive aphasia experience widespread cognitive and behavioural changes that extend beyond language. This evidence, however, seems to be largely ignored or downplayed. This article proposes that linguistic relativity which induces a cognitive bias may be responsible for this omission; it also indicates that a revision of the current diagnostic criteria may need to be revised.

The first report on brain sagging dementia caused by a cranial leak: A case report

ObjectiveBrain Sagging Dementia (BSD) is an increasingly recognized syndrome for which diagnostic criteria recently were proposed. There have been no reports on BSD caused by a cranial leak. Here we present the first report on a patient with BSD caused by a cranial leak.Case descriptionA 60-year old male patient was admitted with a 2-year history of orthostatic headache and gradually progressive cognitive and behavioral changes. Traditional treatments for spontaneous intracranial hypotension, including repeated epidural blood patches, failed. Brain imaging showed severe brain sagging, and intracranial pressure monitoring demonstrated intracranial hypotension. No leakage site was found. His past medical history revealed an accident where a ski pole struck his head at age ten. Due to progressive clinical decline, surgery was pursued. A cranial defect with an accompanying cerebrospinal fluid leak site representing the trauma from his childhood was found and repaired. He also was in need of a ventriculoperitoneal shunt. Following surgery, he improved and recovered completely.DiscussionThis case report illustrates that a cranial leak may cause BSD, even with a “lucid interval” between trauma and symptom debut spanning many years. Moreover, this report validates well the recently proposed BSD diagnostic criteria.

1277P The role of palliative care in patients with glioblastoma multiforme: A single centre review

Patients with Glioblastoma Multiforme (GBM) have a prognosis of 16-21 months and high care needs due to progressive neurological deficits, cognitive impairment, and behavioural change. They often do not express the usual symptoms generally associated with advanced incurable cancer. They therefore represent a challenge to the classic palliative care assessment of needs. We aim to review patients with GBM who were referred to a hospital specialist palliative care (HSPC) service in a quaternary centre to inform service development.

Right Temporal Lobe Variant of Frontotemporal Dementia: Systematic Review.

Frontotemporal dementia corresponds to a heterogenous group of syndromes characterized by progressive changes in behavior and/or language. Approximately 30% of patients with primary progressive aphasia, semantic variant (semantic dementia), present with atrophy in the right cerebral hemisphere, in a rare clinical condition called right temporal variant of frontotemporal dementia (rtvFTD). The objective of the study is to present the main demographic, clinical, neuropsychological, neuroimaging, and pathologic characteristics of rtvFTD patients. A systematic review of the literature was carried out in the PubMed, LILACS, and SCIELO databases between January and March 2022. After the evaluation process, 41 articles were selected, published between 1993 and 2021. We found that rtvFTD presents with severe and progressive prosopagnosia (related to anterior temporal lobe injury) associated with behavioral symptoms-desinibition (51%), apathy (39%), obsessive-compulsive symptoms (37%), changes in eating habits (33%), and depression (28%), which is different from semantic dementia. The most common pathologic pattern is TDP-43, type C. This field of knowledge has few studies (mainly reports and case series) and heterogenous nomenclature, which is a limitation. A multinational longitudinal registry of people with rtvFTD, with standardized assessment and description of symptoms, is necessary to elucidate the characteristics of this entity.

Anti-IgLON5 antibodies cause progressive behavioral and neuropathological changes in mice

BackgroundAnti-IgLON5 disease is a rare neurological disorder associated with autoantibodies against the neuronal cell adhesion protein, IgLON5. Cellular investigations with human IgLON5 antibodies have suggested an antibody-mediated pathogenesis, but whether human IgLON5 autoantibodies can induce disease symptoms in mice is yet to be shown. Moreover, the effects of anti-IgLON5 autoantibodies on neurons and the precise molecular mechanisms in vivo remain controversial.MethodsWe investigated the effects of anti-IgLON5 antibodies in vivo and evaluated their long-term effects. We used two independent passive-transfer animal models and evaluated the effects of the antibodies on mouse behaviors at different time points from day 1 until day 30 after IgG infusion. A wide range of behaviors, including tests of locomotion, coordination, memory, anxiety, depression and social interactions were established. At termination, brain tissue was analyzed for human IgG, neuronal markers, glial markers, synaptic markers and RNA sequencing.ResultsThese experiments showed that patient’s anti-IgLON5 antibodies induced progressive and irreversible behavioral deficits in vivo. Notably, cognitive abnormality was supported by impaired average gamma power in the CA1 during novel object recognition testing. Accompanying brain tissue studies showed progressive increase of brain-bound human antibodies in the hippocampus of anti-IgLON5 IgG-injected mice, which persisted 30 days after the injection of patient’s antibodies was stopped. Microglial and astrocyte density was increased in the hippocampus of anti-IgLON5 IgG-injected mice at Day 30. Whole-cell voltage clamp recordings proved that anti-IgLON5 antibodies affected synaptic homeostasis. Further western blot investigation of synaptic proteins revealed a reduction of presynaptic (synaptophysin) and post-synaptic (PSD95 and NMDAR1) expression in anti-IgLON5 IgG-injected mice.ConclusionsOverall, our findings indicated an irreversible effect of anti-IgLON5 antibodies and supported the pathogenicity of these antibodies in vivo.

Psychosis as a Possible Prodrome of Multiple Sclerosis: A Case Report

AimsMultiple sclerosis (MS) is an autoimmune disease characterized by focal demyelinating lesions that can affect any part of the central nervous system. The highlight of the disease is the wide range of neurological deficits; however, psychiatric manifestations are not uncommon. MS is associated with psychiatric comorbidities, such as depression and anxiety disorders. This is due to either its disease process or its therapies that have been well documented in the literature. However, the link between psychosis as a prodrome and MS remains understudied and relatively uncommon.MethodsWe present a 40-year-old gentleman who developed isolated psychiatric manifestations for about 10 years in the form of progressive behavioral changes, social and occupational dysfunction, coupled with persecutory delusions. No personal or family history of mental illnesses. He was diagnosed and treated as a case of schizophrenia by a psychiatrist with multiple antipsychotics with a minimal improvement of his symptoms. Three months before our assessment the patient had a history of difficulty walking associated with urine and fecal incontinence. On examination, he had restricted affect and was easily agitated. Neurological examination revealed hypertonia and hyperreflexia in his left upper and lower limbs with normal power bilaterally. T2-weighted magnetic resonance imaging (MRI) brain showed multiple non-enhancing characteristic demyelinating lesions with typical shape and distribution. Further work-up was done to confirm the diagnosis of MS and exclude differentials, including a negative autoimmune screen, anti-aquaporin-4 (AQP4), and Myelin oligodendrocyte glycoprotein (MOG) antibodies. Visual evoked potentials documented bilateral severe disturbance in the visual pathway in both eyes, suggesting axonal loss. The patient is a candidate for a disease-modifying therapy for MS. Natalizumab or Ocrelizumab was selected based on his clinical criteria and will be started after proper preparation.ResultsPsychiatric comorbidities in MS are associated with reduced compliance to disease-modifying therapies and lower quality of life. Studies reported that lesions in the periventricular area in the temporal region may be associated with psychosis, but not as an isolated presentation in patients with MS.ConclusionMS is one of the differentials of psychotic disorder due to a medical condition, and rarely may present with pure psychiatric manifestations preceding any obvious neurological deficits, leading to delay in the diagnosis. Despite being uncommon, a high index of suspicion should be kept in patients with atypical presentations associated with limited response to multiple antipsychotics. This highlights the importance of conducting a thorough physical examination and work-up to exclude an organic pathology, necessitating proper management.

Unusual neurological presentation of second stage African trypanosomiasis in a young boy: a case report

BackgroundIn South Sudan, sleeping sickness is a frequent condition caused by human African trypanosomiasis. There are two stages that are well-known. When the CNS is affected, especially with Trypanosoma gambiense infection, the early hemolymphatic stage and the late encephalitic stage have been observed, including mental, motor, and sensory symptoms. In this case, second-stage African trypanosomiasis manifested itself in an atypical neurological manner.Case presentationA 16-year-old boy from South Sudan referred to Sudan National Centre for Neurological Sciences, Khartoum, Sudan suffering from non-convulsive status epilepticus, mental deterioration and behavioral changes for the last nine months. He was conscious but disorientated. Low hemoglobin concentration, elevated ESR, enlarged spleen and positive card agglutination test for trypanosomiasis was found in this patient. Electro-encephalogram (EEG) found an on-going generalized seizure activity. The patient showed improvement after management with carbamazepine and tonic.ConclusionOur case highlights that late second stage African trypanosomiasis with neurological complications such as non-convulsive status epilepticus should be suspected in any patient who developed progressive cognitive decline and behavioral changes following long standing history of African Trypanosomiasis and routine Electro-encephalogram EEG is the best tool to diagnose non convulsive status epilepticus.

Sporadic Creutzfeldt-Jakob Disease Presenting with Rapidly Progressing Dementia – A Family Medicine Perspective of Two Case Reports

Dementia is an increasing problem in Singapore’s ageing population with the most common being Alzheimer’s disease, vascular dementia, and mixed dementia. Creutzfeldt-Jakob Disease (CJD) is a fatal neurodegenerative condition that causes rapidly progressive dementia. It is a rare human transmissible prion disease with limited literature in Southeast Asia. In this article, we report 2 patients diagnosed with CJD who presented to primary care with rapidly progressive dementia, behavioral changes, and rapid functional decline. Deterioration of their clinical condition was relentless, and treatment remained palliative and supportive. It is important for family physicians to be cognisant of the clinical manifestations of CJD. We will outline the role of family physicians in the management of patients with CJD in different healthcare settings – general practice, tertiary hospital, community hospital and hospice home care.

Brain Sagging Dementia-Diagnosis, Treatment, and Outcome: A Review.

Brain sagging dementia (BSD), caused by spontaneous intracranial hypotension (SIH), is a rare syndrome that is only recently recognized, mimicking the clinical findings of behavioral variant frontotemporal dementia (bvFTD). Being aware of its signs and symptoms is essential for early diagnosis and treatment in this potentially reversible form of dementia. Our objective was to identify cases of BSD in the literature and present its clinical characteristics, diagnostic workup, treatment options, and outcome. The review was reported according to PRISMA guidelines and registered with the PROSPERO database (CRD42020150709). MEDLINE, EMBASE, PsychINFO, and Cochrane Library were searched. There was no date restriction. The search was updated in April 2021. A total of 983 articles were screened and assessed for eligibility. Twenty-nine articles (25 case reports and 4 series) and 70 patients were selected for inclusion. No cranial leak cases were identified. BSD diagnosis should be made based on clinical signs and symptoms and radiologic findings. There is a male predominance (F:M ratio 1:4) and a peak incidence in the 6th decade of life. The main clinical manifestation is insidious onset, gradually progressive cognitive and behavioral changes characteristic for bvFTD. Headache is present in the majority of patients (89%). The presence of brain sagging and absence of frontotemporal atrophy is an absolute criterion for the diagnosis. CSF leak is identified with myelography and digital subtraction myelography. The treatment and repair depend on the etiology and extent of the dural defect, although an epidural blood patch is the first-line treatment in most cases. With treatment, 81% experienced partial and 67% complete resolution of their symptoms. This review highlights the most important clinical aspects of BSD. Due to the sparse evidence and lack of BSD awareness, many patients are likely left undiagnosed. Recognizing this condition is essential to provide early treatment to reverse the cognitive and behavioral changes that may otherwise progress and fully impair the patient. Moreover, patients with longstanding SIH must be assessed carefully for cognitive and behavioral changes.

Chapter 24 - Frontotemporal dementia: A unique window on the functional role of the temporal lobes

Frontotemporal dementia (FTD) is an umbrella term covering a plethora of progressive changes in executive functions, motor abilities, behavior, and/or language. Different clinical syndromes have been described in relation to localized atrophy, informing on the functional networks that underlie these specific cognitive, emotional, and behavioral processes. These functional declines are linked with the underlying neurodegeneration of frontal and/or temporal lobes due to diverse molecular pathologies. Initially, the accumulation of misfolded proteins targets specifically susceptible cell assemblies, leading to relatively focal neurodegeneration that later spreads throughout large-scale cortical networks. Here, we discuss the most recent clinical, neuropathological, imaging, and genetics findings in FTD-spectrum syndromes affecting the temporal lobe. We focus on the semantic variant of primary progressive aphasia and its mirror image, the right temporal variant of FTD. Incipient focal atrophy of the left anterior temporal lobe (ATL) manifests with predominant naming, word comprehension, reading, and object semantic deficits, while cases of predominantly right ATL atrophy present with impairments of socioemotional, nonverbal semantic, and person-specific knowledge. Overall, the observations in FTD allow for crucial clinical-anatomic inferences, shedding light on the role of the temporal lobes in both cognition and complex behaviors. The concerted activity of both ATLs is critical to ensure that percepts are translated into concepts, yet important hemispheric differences should be acknowledged. On one hand, the left ATL attributes meaning to linguistic, external stimuli, thus supporting goal-oriented, action-related behaviors (e.g., integrating sounds and letters into words). On the other hand, the right ATL assigns meaning to emotional, visceral stimuli, thus guiding socially relevant behaviors (e.g., integrating body sensations into feelings of familiarity).

Progressive Cognitive and Behavioral Changes With Leukodystrophy due to ABCD1 Gene Mutation

Progressive Cognitive and Behavioral Changes With Leukodystrophy due to <i>ABCD1</i> Gene Mutation

SSPE (SUBACUTE SCLEROSING PANENCEPHALITIS) - THE GREAT MASQUERADER

Background: SSPE is chronic progressive encephalitis affecting children and young adults which usually presents with cognitive decline and behavioural changes followed by periodic myoclonic jerks, seizures, vision loss and ataxia. High degree of suspicion is required as the presentation can be variable and can have many differentials. Aim: We aim to study various presentations of SSPE Methods and Material: Retrospective study was done to analyse various presentations in patients diagnosed with SSPE as per modied Dykens criteria from a tertairy care centre over a period of 2 years (1st January 2018-31st December 2020). Results: 6 cases of SSPE were identied. Case1 - 22 months old presented with subacute history of ataxia, multical myoclonus and developmental regression. Gradually myoclonus worsened to involve trunk and developed drop attacks. Case 2 - 17 years boy presented with single episode of seizure. Case 3- 25 years female with 5 months gestation presented with subacute vision loss followed by progressive cognitive decline, behavioural changes, Parkinsonism, Dystonia and stimulus sensitive myoclonus. Case4- 28 years female presented with rapidly progressive cognitive decline and behavioural changes. Case 5- 32 years male presented with history of myoclonic jerks and dropping of objects. Gradually developed progressive behavioural changes and cognitive decline and became vegetative. Case6 - 9 year old child presented with faciobrachial seizures (myoclonic jerks) and scholastic backwardness. Conclusions: SSPE can manifest with varied presenting complaints. Also, Results of EEG, MRI and CSF examination can change during the disease course. Therefore, high degree of suspicion is required for early diagnosis of this challenging entity.