A Systematic Review of the Genetics and Pathology of Psychosis in Frontotemporal Dementia.

OBJECTIVES: Frontotemporal dementia (FTD) patients frequently present with psychosis, which complicates diagnosis and management. In this study, we aim to examine the relationship between psychosis and the most common genetic mutations predisposing to FTD, and in the different pathological subtypes of FTD. DESIGN: We conducted a systematic review, searching the literature up to December 2022, and reviewed 50 articles that met our inclusion criteria. From the reviewed articles, we extracted and summarized data regarding the frequency of psychosis and patient characteristics in each major genetic and pathological subtype of FTD. RESULTS: Among FTD patients with confirmed genetic mutations or pathological diagnosss, the frequency of psychosis was 24.2%. Among the genetic mutation carriers, C9orf72 mutation carriers had the highest frequency of psychosis (31.4%), whereas GRN (15.0%) and MAPT (9.2%) mutation carriers had lower frequencies of psychosis. MAPT mutation carriers notably developed psychosis at a younger age compared to other genetic groups. The most common psychotic symptoms were delusions among C9orf72 carriers and visual hallucinations among GRN mutation carriers. Among the pathological subtypes, 30% of patients with FUS pathology, 25.3% of patients with TDP-43 pathology, and 16.4% of patients with tau pathology developed psychosis. In the TDP-43 group, subtype B pathology was the most common subtype reported in association with psychosis. CONCLUSION: Our systematic review suggests a high frequency of psychosis in specific subgroups of FTD patients. Further studies are required to understand the structural and biological underpinnings of psychosis in FTD.

Clinico-pathological comparison of patients with autopsy-confirmed Alzheimer's disease, dementia with Lewy bodies, and mixed pathology.

INTRODUCTION: Patients with Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) frequently demonstrate coexistent AD neuropathological change (ADNC) and Lewy body pathology (LBP) at autopsy. We investigated the effects of ADNC and LBP on the clinical presentation of these patients. METHODS: We retrospectively compared clinical and pathological features of patients with different severity of ADNC and LBP. We also compared the burden of medullary LBP between patients with and without autonomic dysfunction. RESULTS: Compared to pure ADNC, patients with AD/LBP have higher prevalence of DLB symptoms. Autonomic dysfunction strongly predicted the presence of LBP in patients with clinically diagnosed AD, but was not associated with increased LBP burden in the medulla. Severity of ADNC, but not LBP, was associated with cerebral atrophy. DISCUSSION: Clinical presentation of patients with AD/LBP differs from patients with pure ADNC or LBP. Autonomic dysfunction is a useful marker of otherwise unsuspected LBP.

CCCDTD5 recommendations on early and timely assessment of neurocognitive disorders using cognitive, behavioral, and functional scales.

INTRODUCTION: Earlier diagnosis of neurocognitive disorders and neurodegenerative disease is needed to implement preventative interventions, minimize harm, and reduce risk of exploitation in the context of undetected disease. Along the spectrum from subjective cognitive decline (SCD) to dementia, evidence continues to emerge with respect to detection, staging, and monitoring. Updates to previous guidelines are required for clinical practice. METHODS: A subcommittee of the 5th Canadian Consensus Conference on Diagnosis and Treatment of Dementia (CCCDTD) reviewed emerging evidence to address the following: (1) Is there a role for screening at-risk patients without clinical concerns? In what context is assessment for dementia appropriate? (2) What tools can be used to evaluate patients in whom cognitive decline is suspected? (3) What important information can be gained from an informant, using which measures? (4) What instruments can be used to get more in-depth information to diagnose mild cognitive impairment (MCI) or dementia? (5) What is the approach to those with cognitive concerns but without objective changes (ie, SCD)? (6) How do we track response to treatment and change over time? The Grading of Recommendations Assessment, Development, and Evaluation system was used to rate quality of the evidence and strength of the recommendations. RESULTS: We recommend instruments to assess and monitor cognition, behavior, and function across the cognitive spectrum, including reports from patient and informant. We recommend against screening asymptomatic older adults but recommend investigation for self- or informant reports of changes in cognition, emergence of behavioral or psychiatric symptoms, or decline in function or self-care. Standardized assessments should be used for cognitive and behavioral change that have sufficient validity for use in clinical practice. DISCUSSION: The CCCDTD5 provides evidence-based recommendations for detection, assessment, and monitoring of neurocognitive disorders. Although these guidelines were developed for use in Canada, they may also be useful in other jurisdictions.

Calvarial Tuberculosis in a Preschool-Aged Child: An uncommon entity.

Calvarial tuberculosis is a rare manifestation of tuberculosis, especially in children under five years of age. We report a two-and-a-half-year-old male child who presented to the Nilratan Sircar Medical College, Kolkata, India, in 2015 with frontoparietal fluctuant swelling of three months' duration. He had also had chronic sinus discharge from the left lower eyelid over the previous six months. Computed tomography of the head revealed a frontal swelling along with erosion of both the outer and inner plates of the left frontal bone. Fine needle aspiration of the pus indicated the presence of acid-fast bacilli. Unfortunately, no primary focus of tuberculosis could be established. The patient improved after one year of antitubercular therapy without requiring any surgical intervention and with no sign of subsequent disease recurrence.

Correlation of intracranial atherosclerosis with carotid stenosis in ischemic stroke patients.

INTRODUCTION: Carotid stenosis is a major risk factor for ischemic stroke. However, the effect of carotid stenosis on the site of stroke is still under investigation. AIMS: This study aimed to elucidate how the presence of carotid stenosis influenced the pattern of stroke and also how it interacted with other risk factors for stroke. MATERIALS AND METHODS: Thirty-eight patients with ischemic stroke were included in this study and were investigated with carotid artery Doppler and magnetic resonance angiography for carotid stenosis and intracranial stenosis in the circle of Willis, respectively. Other known risk factors of stroke were also studied in and compared between the subgroups with and without carotid stenosis. RESULTS: In patients without carotid stenosis, anterior cerebral artery was the commonest site of stenosis. In patients with carotid stenosis, middle cerebral artery was the commonest site of stenosis. Overall, middle cerebral artery was the commonest territory of stroke. Patients with hypertension, diabetes and history of smoking had preferential stenosis of the anterior cerebral artery.

Cerebellar ataxia in a young patient: A rare path to lupus.

Cerebellar ataxia is a rare manifestation of neuropsychiatric systemic lupus erythematosus (SLE). Development of vasculitic infarcts in the cerebellum is the most plausible reason of this manifestation. We report the case of a patient who presented with characteristic skin rashes of lupus along with cerebellar signs. Imaging of brain in this patient revealed prominent cerebellar atrophy. She was treated with mycophenolate mofetil and oral corticosteroid, and there was no further progression of her neurological signs after the initiation of therapy. In the clinical context of varied presentations of neurolupus, this is one of the rare sightings and our treatment protocol holds promise as first-line therapy in future.

Lambda light chain myeloma presenting as nodular hepatic lesion: a clinical rarity.

We report a case of a 63-year-old lady presenting with pain in the right hypochondrium, jaundice, anorexia, and firm tender hepatomegaly with remarkably high serum alkaline phosphatase. Abdominal ultrasonography revealed a hypoechoic solid space-occupying lesion in right lobe of liver which was cytologically diagnosed as hepatic plasmacytoma. Serum and urine immunofixation electrophoresis, serum free light chain ratio, and bone marrow examination further confirmed the presence of lambda light chain multiple myeloma in the background. The patient achieved complete remission after four cycles of induction therapy with thalidomide and dexamethasone protocol and consolidated with further four cycles of the same regimen.

Glutamate-based magnetic resonance spectroscopy in neuroleptic malignant syndrome.

Glutamate neurotoxicity is implicated in a number of neurological diseases, including Neuroleptic Malignant syndrome. Therefore, functional magnetic resonance imaging can help in diagnosis and monitoring such conditions. However, reports of this application are scarce in the literature. In this manuscript, glutamate based imaging of the basal ganglia showed increased levels of the neurotransmitter bilaterally. In addition, a radon transform of the functional image was performed to look for any asymmetry in cerebral activation. Although no asymmetry was detected in this case, this novel analysis can be applied in physiological and pathological scenarios to visualize contribution of different brain structures.

Altered levels of amyloid precursor protein intracellular domain-interacting proteins in Alzheimer disease.

BACKGROUND: The amyloid precursor protein intracellular domain (AICD) is an intrinsically unstructured molecule with functional promiscuity that plays an important role in determining the fate of the neurons during its degeneration. Its association with Alzheimer disease (AD) recently played a key role in propelling scientists to choose AICD as a major molecule of interest. Although several studies have been conducted elucidating AICD's participation in inducing neurodegenerative outcomes in AD condition, much remains to be deciphered regarding the linkage of AICD with cellular pathways in the AD scenario. RESULTS: In the present study, we have pulled down interactors of nonphosphorylated AICD from the cerebrospinal fluid of AD subjects, identified them by matrix assisted laser desorption ionization mass spectrometry, and subsequently studied the differential expression of these interactors in AD and control cases by 2-dimensional difference gel electrophoresis. The study has yielded some AICD-interactors that are differentially expressed in the AD cases and are involved in diverse cellular functions. CONCLUSIONS: This proteomic-based approach highlights the first step in finding the possible cellular pathways engaged in AD pathophysiology on the basis of interaction of one or more of their members with AICD.

A commonly overlooked motor neuron disease mimicker.

UNLABELLED: Motor neuron disease (MND) is a progressive devastating neurodegenerative disease, which universally progresses towards death. Hence, every attempt should be made to find out if there are any treatable conditions, which can mimic MND. Herein, we describe a case of hypercalcaemia due to primary hyperparathyroidism confused as MND and subsequently cured with parathyroid surgery. LEARNING POINTS: Any patient with neurological disorder should have a screening of all the common electrolytes including calcium as electrolyte imbalance can present with paralysis (e.g. hypokalaemia) to amyotrophic lateral sclerosis (e.g. hypercalcaemia).No patient should be stamped as having MND without having a proper work-up of all its differentials as there might be a treatable condition masquerading as MND.

Tropical pyomyositis.

BACKGROUND: Tropical pyomyositis is characterized by suppuration within skeletal muscles, manifesting as single or multiple abscesses. Though primarily a disease of tropics, it is increasingly being reported from temperate regions in immunosuppressed patients. However, India has only few sporadic case reports. AIMS: The aim of this study is to evaluate the causative organisms, clinical presentations, diagnostic modalities, treatment protocols and outcome data in tropical pyomyositis patients. SUBJECTS AND METHODS: The study was carried out in Nilratan Sircar Medical College and Hospital, Kolkata over 3 years (July 2010 to June 2013). A total of 12 patients were diagnosed with tropical pyomyositis (confirmed with aspiration and culture of pus from muscle). All the investigation and treatment data were recorded systematically. RESULTS: The presenting feature was high fever and myalgia in all 12 patients. Quadriceps femoris was the most commonly involved muscle (50%); followed by iliopsoas (25%). Culture of the aspirate showed Staphylococcus aureus in nine patients (75%), Klebsiella pneumonia in one patient (8.33%) and no growth in two patients (16.67%) even after tubercular and fungal culture. CONCLUSIONS: Tropical pyomyositis can affect immune-competent individuals. S. aureus is the most commonly cultured organism. Immediate initiation of appropriate antibiotics and surgical debridement are required to avoid complications. The prognosis remains excellent if promptly treated.

Seizure, deafness and renal agenesis: A rare case of barakat syndrome.

Etiologic diagnosis of seizure requires proper consideration of apparently unrelated clinical features of the patient. Here, we report the case of a patient of status epilepticus with moderate-to-severe bilateral sensorineural deafness. Investigations showed extensive intracranial calcification, hypoparathyroidism and unilateral renal agenesis. The features were consistent with Barakat syndrome, a rare developmental disorder associated with mutations in the GATA3 gene. To the best of our knowledge, this is the first reported case of Barakat syndrome from India.

Rare presentation of a common disease: Idiopathic hypoparathyroidism presenting with extrapyramidal symptoms and status epilepticus.

We report of an 18-year-old male who presented with an epileptiform disorder, features of hypocalcemia, and an extrapyramidal symptom in the form of choreoathetosis. On evaluation he had idiopathic hypoparathyroidism with extensive calcifications in the extrapyramidal system of the brain; basal ganglion, as well as in the cerebral cortex and cerebellum, which is a rare entity. We report the rare presentation of a common disorder, which requires to be considered in evaluating hypoparathyroidism.

Whistle from afar: a case of endotracheal metastasis in papillary thyroid cancer.

Endotracheal metastasis is a rare situation, usually associated with malignancies of breast and gastrointestinal tract, specially colon. Papillary carcinoma of thyroid commonly disseminates through lymphatic channels and tracheal involvement through vascular route is rarely reported. Here, we report a case of tracheal metastasis from papillary carcinoma of thyroid. The patient responded to external beam radiation therapy with cobalt 60 beams in a dose of 44 Gy followed by a 16 Gy boost. The patient is under followup and is presently asymptomatic. This paper adds to the repertoire of evidence in treatment of endotracheal metastasis.

Stroke and skin rash: A rare case of Henoch-Schonlein purpura.

Henoch-Schonlein purpura (HSP) is a small vessel vasculitis that is rare in adults. Here, we present a case of a woman who presented with palpable purpura, abdominal pain, arthritis and ischemic stroke. The patient met the diagnostic criteria of HSP. However, cerebrovascular disease is reported as an uncommon, yet fatal, complication of HSP. The patient responded to aggressive immunosuppression with pulses of corticosteroids and cyclophosphamide. In the absence of an established protocol of treatment of such neurologic emergency in HSP patients, this report demonstrates a successful outcome.