Neurological Signs Research Articles

Evaluating the efficacy of a ketogenic diet in managing drug resistant paediatric DEDPC5-related epilepsy

AimTo evaluate the effectiveness of the ketogenic diet treatment in a cohort of patients with drug-resistant epilepsy with a mutation in the DEPDC5 gene. Materials and MethodsWe followed four paediatric patients with drug resistant DEPDC5-related epilepsy through a ketogenic diet (KD) treatment course. We analyzed the following parameters of their clinical profiles: past medical history, clinical characteristics of seizure morphology, EEG records pre- and post-KD treatment, the results of MRI head and neurological and psychological examinations (pre-treatment and throughout treatment course). We evaluated the effectiveness of previous therapeutic approaches and the current treatment with ketogenic diet alongside results of neuroimaging studies. Effect of KD on co-morbid behavioural and psychiatric symptoms, as well as adverse effects from KD were also assessed. ResultsIn three patients, the introduction of the ketogenic diet resulted in the cessation of seizures, while in 1 patient with co-morbid cortical dysplasia, epileptic seizures of lesser severity returned after an initial seizure-free period of several weeks. Further, 1 patient was able to transition to a KD-only treatment regimen. The remaining patients were able to reduce the number of antiseizure medicine (ASM) to a monotherapy. In all cases we observed improvements in EEG results. Our cohort included one patient whose MRI head showed cortical dysplasia. However, no patients demonstrated any neurological signs in neurological examination. Psychological examination showed normal intellectual development in all patients, although behavioral disorders and difficulties at school were observed. The introduction of KD treatment correlated with improvement in school performance and improved behavioral regulation. No clinically significant adverse events were observed. ConclusionsKD seems to be both effective and well tolerated in young patients with DEPDC5-related epilepsy, both as a monotherapy and as an adjunct to ASM. We recommend an early adoption of this therapeutic approach in this patient demographic. Our results demonstrate that the positive effects of KD treatment encompass improvements in general functioning, particularly in the context of school performance and behavior, in addition to the achievement of good seizure control.

Detection of a new avian bornavirus in barn owl (Tyto alba) by pan-viral microarray

A barn owl (Tyto alba) died with neurological signs compatible with a viral infection. After discarding other possible infections caused by circulating viruses in the area, analysis of the central nervous system using a pan-viral microarray revealed hybridization to canary bornavirus 2 (CnBV-2). Subsequent sequence analysis confirmed the presence of a virus sharing more than 83% identity with CnBV-2. Surprisingly, the new sequence corresponds to a new virus, here named Barn owl Bornavirus 1 (BoBV-1), within the Orthobornavirus serini species. Moreover, it is the first member of this species that has been detected in a non-passerine bird, indicating that Orthobornavirus serini species comprises viruses with a wider range of hosts than previously presumed. The use of this microarray has proven to be an excellent tool for viral detection in clinical samples, with capacity to detect new viral variants. This allows the diagnosis of a great range of viruses, which can cause similar disease symptoms and which identification by PCR methods might be tedious, probably unsuccessful and, in the long run, expensive. This platform is highly useful for a fast and precise viral detection, contributing to the improvement of diagnostic methods.

Circulating biomarkers in familial cerebral cavernous malformation

BackgroundCerebral Cavernous Malformation (CCM) is a rare cerebrovascular disease, characterized by the presence of multiple vascular malformations that may result in intracerebral hemorrhages (ICH), seizure(s), or focal neurological deficits (FND). Familial CCM (fCCM) is due to loss of function mutations in one of the three independent genes KRIT1 (CCM1), Malcavernin (CCM2), or Programmed Cell death 10 (PCDC10/CCM3). The aim of this study was to identify plasma protein biomarkers of fCCM to assess the severity of the disease and predict its progression. MethodsHere, we have investigated plasma samples derived from n=71 symptomatic fCCM patients (40 female/31 male) and n=17 healthy donors (HD) (9 female/8 male) of the Phase 1/2 Treat_CCM trial, using multiplexed protein profiling approaches. FindingsBiomarkers as sCD14 (p= 0.00409), LBP (p= 0.02911), CXCL4 (p= 0.038), ICAM-1 (p= 0.02013), ANG2 (p= 0.026), CCL5 (p= 0.00403), THBS1 (p= 0.0043), CRP (p= 0.0092), and HDL (p= 0.027), were significantly different in fCCM compared to HDs. Of note, sENG (p= 0.011), THBS1 (p= 0.011) and CXCL4 (p= 0.011), were correlated to CCM genotype. sROBO4 (p=0.014), TM (p=0.026) and CRP (p=0.040) were able to predict incident adverse clinical events, such as ICH, FND or seizure. GDF-15, FLT3L, CXCL9, FGF-21 and CDCP1, were identified as predictors of the formation of new MRI-detectable lesions over 2-year follow-up. Furthermore, the functional relevance of ang2, thbs1, robo4 and cdcp1 markers was validated by zebrafish pre-clinical model of fCCM. InterpretationOverall, our study identifies a set of biochemical parameters to predict CCM progression, suggesting biological interpretations and potential therapeutic approaches to CCM disease. FundingItalian Medicines Agency, Associazione Italiana per la Ricerca sul Cancro (AIRC), ERC, Leducq Transatlantic Network of Excellence, Swedish Research Council.

First Swedish case of fatal equine parasitic encephalitis by Halicephalobus gingivalis

BackgroundHalicephalobus gingivalis is a nematode with zoonotic potential which can cause fatal opportunistic infections in various mammals. The parasite has never been diagnosed in Sweden, in any species, prior to the presented case.Case presentationAn imported 21-year-old Icelandic mare developed severe neurological signs. The horse was eventually euthanized and submitted for post-mortem examination where severe lesions in the kidneys were noted. Histopathology revealed the presence of H. gingivalis in both kidneys and the brain. Phylogenetic analysis of the parasite determined it to belong to Lineage 1.ConclusionsWith the occurrence of H. gingivalis in Sweden, the disease should be added to the list of differential diagnoses in cases with acute onset of neurological disease in both horses and other mammals including humans.

Percutaneous coronary intervention in patients admitted with acute coronary syndrome within 6 months after COVID-19 (retrospective single-center study)

BACKGROUND: Assessing clinical manifestations in patients during the period of destabilization of the course of coronary artery disease after COVID-19 coronavirus infection remains a clinical problem. Identifying features of coronary artery lesions in such patients will help to prevent the development of complications and may influence the tactics of active dynamic monitoring.
 AIM: To evaluate the structure of coronary artery lesions and clinical manifestations in patients with acute coronary syndrome that developed within 6 months after COVID-19 new coronavirus infection.
 MATERIALS AND METHODS: A comparative analysis of the results of coronary artery stenting in 157 patients admitted with acute coronary syndrome has been carried out. The 1st group included 69 patients who had COVID-19 (vaccinated — 24.6%) during the 6 months preceding acute coronary syndrome; in the 2nd — 88 patients without a history of COVID-19 (vaccinated — 42%). All the patients had drug-eluting stents implanted in the infarct-related artery. Long-term results have been observed in 151 (96.2%) patients.
 RESULTS: Before the development of acute coronary syndrome, dispnoe was more often observed in patients of the 1st group (36; 52%) than in patients of the 2nd group (13; 14.8%). There were no focal neurological symptoms in the patients of both groups. Dizziness more often preceded acute coronary syndrome in the patients of the 1st group (26; 38.2%) compared to the control group (5; 5.7%). Decreased motivation and fatigue were detected in 27 (67.5%) patients in the 1st group, which was more common than in the 2nd group (13; 32.5%). Acute coronary syndrome with ST elevation was treated in 47 % and 38.6% of the patients in the 1st groups and the 2nd, respectively. The development of acute coronary syndrome with ST segment elevation with previous clinical manifestations of post-covid syndrome in the 1st group was observed in 95.8%, whereas in the absence of post-covid syndrome in 53.3%. The mean value of LVEF in patients who had COVID-19 was 55.9 ± 14%, which was significantly lower than in the patients in the control group (63.2 ± 5.5%; р 0.001). During the course of coronavirus infection in the patients in the first group, lung damage of degrees I–II according to CT scan data was observed in 76.8% of the patients and in 23.2% of degrees III–IV. The frequency of lesions of the circumflex branch in the 1st group was 15.9%, in the 2nd — 11.4% (р = 0.403); of the right coronary artery — 33.3%, and 22.7% (р = 0.41); of the diagonal branch — 5.8%, and 3.4% (р = 0.47); of the left main coronary artery — 5.8%, and 6.8% (р = 0.79), of the left anterior descending branch — 52.2%, and 35.2% (р = 0.033), respectively. The incidence of vasospastic angina in the 1st group was 53.6%, in the 2nd — 15.9% (р 0.0001). ST segment elevation in lead AVR as a manifestation of subendocardial ischemia was registered in the 1st group — 40.6%, the 2nd — 11.4% (р 0.0001). All the patients had drug-eluting stents implanted in the infarct-related artery. Overall survival (in-hospital and long-term) was 100% for the first group and 100 % for the second one.
 CONCLUSIONS: In the structure of coronary arteries lesions after COVID-19 new coronavirus infection in patients with acute coronary syndrome, damage to the anterior interventricular artery dominates (52.2%). The likelihood of having a left anterior descending lesion during the development of acute coronary syndrome with ST segment elevation in patients who have had COVID-19 is 1.5 times higher. The structure of clinical manifestations after COVID-19 in patients before the development of acute coronary syndrome is dominated by shortness of breath (52 %) and decreased motivation and fatigue (67.5 %).

Tuberous sclerosis complex, Clinic and pathology manifestations, Mini -review

Tuberous sclerosis complex (TSC) is an autosomal dominant neurocutaneous syndrome that affects almost all of the organs of the body, including the brain, heart, lungs, liver, and kidneys. Brain tumors in TSC patients include cortical tubers, subependymal nodules (SENs), and Subependymal giant cell astrocytomas (SEGAs). Seizures that occur in 92% of patients with TSC are an important cause of sudden deaths in them. Other organ involvement includes renal angiomyolipomas, lymphangioleiomyomatosis, cardiac rhabdomyomas, and cutaneous manifestations (hypomelanotic macules, angiofibroma, ungual fibromas, shagreen patch, and ‘confetti’ skin lesions). There is a criterion for tuberous sclerosis complex that consists of 11 major and 6 minor clinical features that diagnosis occurs based on it. The best way for a definitive diagnosis of TSC in a patient is by using genetic tests and histopathology. Immunohistochemistry is a helpful method in confirming the diagnosis of brain tumors in TSC. Immunostaining of SEGA shows positivity for GFAP and S-100 protein while neurofilament and synaptophysin are negative. Ki-67, which indicates nuclear proliferation, has a low proliferation index in immunostain. In an aggressive tumor, hydrocephalus, rising intracranial pressure and focal neurologic deficit, surgery is a necessity and can improve outcomes. Brain and kidney involvement in this disease is life-threatening. Brain involvement in these patients can lead to extensive neuropsychological complications, so the aim of this study is a concise review of the variable manifestations of this disease with a focus on the histopathological findings of brain involvement.

Case report: Acute audiovestibular presentation following hemi-pontine infarction

Posterior circulation stroke is an uncommon cause of sudden-onset sensorineural hearing loss (SSNHL). Anterior inferior cerebellar artery occlusion results in ipsilateral peripheral audiovestibular dysfunction. Few reports describe posterior circulation stroke presenting with contralateral SSNHL and acute vestibular and focal neurological signs. We present a case of contralateral SSNHL and isolated acute central vestibular dysfunction in the absence of other central focal neurological deficits. To the best of our knowledge, this has not been described to date. The patient was identified to have asymmetrical SSNHL, subtle skew deviation with left head tilt, and significant refixation saccades on video head impulse test despite bilaterally normal vestibulo-ocular reflex gains. Left pontine infarct was suspected and confirmed on magnetic resonance imaging. The patient was treated with an appropriate antiplatelet regimen. We highlight the importance of a thorough clinical diagnostic work-up as posterior circulation strokes with isolated audiovestibular deficits can be easily missed if other significant neurological deficits are absent.

PHYSICAL THERAPY AND NEUROREHABILITATION OF PATIENTS WITH CEREBROVASCULAR STROKE

Cerebral stroke represents an acute disturbance of circulation in the brain, which occurs with local and general brain symptoms. Main etiological factors are: arteriosclerosis, increased blood pressure, arterial hypotension, heart diseases, malformations of brain blood vessels, etc. Stroke is the most common neurological disease and the leading cause of mortality in the world, right after cardiovascular and malignant diseases. Cerebrovascular stroke is a focal neurological deficit caused by intracerebral hemorrhage. It is a condition that occurs due to a change in blood circulation in the brain and a very low supply of oxygen and nutrients to parts of the brain, which results in their damage and disruption of the functions that depend on them. There are two types of cerebrovascular stroke: ischemic - thrombosis and thromboembolism (85%) and hemorrhagic – intracerebral and subarachnoid bleeding (15%). The clinical picture can develop gradually or, the patient can suddenly fall into a coma. Absence of movements of the affected limbs predominates, always opposite to the side of the impact with an outburst of the facial nerve of the central type. Hemiplegia is a loss of the voluntary movements of one half of the body, caused by damage to the opposite brain hemisphere. The musculature is atonic, tendon reflexes are reduced or lost. The aim of the research is to determine the effectiveness of physical therapy and neurorehabilitation in patients with cerebrovascular brain stroke. Treatment of stroke: In the acute stage, physical therapy is aimed at preventing complications of the loco-motor apparatus (contractures, muscle and tendon retraction, heterotropic ossifications), the respiratory system (hypostatic pneumonia) and the skin (decubitus). This is achieved through treatment with position (frequent change of the position of the body in bed), passive exercises performed according to strictly defined rules, breathing exercises, exercises for healthy limbs and great care of the skin. The trophic changes of the skin are treated with ultraviolet radiation in suberythemic doses or with D’Arsonval currents. The research was conducted at the University of Southeast Europe - (Stul University) at the Faculty of Health Sciences in the Department of Physical Therapy and Rehabilitation, over a period of 6 months, from the beginning of From the beginning of May - to the end of October 2023. The research included 27 stroke patients, of which 11 patients had a left-sided stroke, and the remaining 14 patients had a right-sided stroke. According to the gender structure, 12 patients are male and the remaining 15 patients are female. After completing the six-month treatment with physical therapy, kinesitherapy and the methods of Vojta and Carl and Bertha Bobat, the results show great progress in almost all parameters. A decrease in tonic primitive reflexes, neck and labyrinthine tonic reflexes, reduction of extensor hypertonia, improvement of motor-reflex activity, proprioceptive afference, coordination, reduction of neck tone, foot reflex, stimulation of the grip reflex and improvement of the position of the neck, limbs and body. The presented results shows significant improvement in both groups of participants. Physical therapy and rehabilitation combined with kinesitherapy have an exceptional positive effect in: prevention of pathological primitive reflexes;creation and automation of normal active movements;saving irregular positions of the limbs and the whole body;establishment of balance and correct pattern of movement; fight against spasticity, secondary contractures and deformities; improvement of coordination and awareness of the body in relation to the environment.

Neurologic involvement in cystinosis: Focus on brain lesions and new evidence of four-repeat (4R-) Tau immunoreactivity

Nephropathic cystinosis is a rare autosomal recessive storage disorder caused by CTNS gene mutations, leading to autophagy-lysosomal pathway impairment and cystine crystals accumulation. Neurologic involvement is highly variable and includes both neurodevelopmental and neurodegenerative disturbances, as well as focal neurologic deficits. By presenting longitudinal data of a 28-year-old patient with a large infratentorial lesion, we summarized the pathology, clinical and imaging features of neurological involvement in cystinosis patients. Brain damage in form of cystinosis-related cerebral lesions occurs in advanced disease phases and is characterized by the accumulation of cystine crystals, subsequent inflammation with vasculitis-like features, necrosis, and calcification. Epilepsy is a frequent comorbidity in affected individuals. Steroids might play a role in the symptomatic treatment of “stroke-like” episodes due to edematous-inflammatory lesions, but probably do not change the overall prognosis. Lifelong compliance to depleting therapy with cysteamine still represents the main therapeutic option. However, consequences of CTNS gene defects are not restricted to cystine accumulation. New evidence of four-repeat (4R-) Tau immunoreactivity suggests concurrent progressive neurodegeneration in cystinosis patients, highlighting the need of innovative therapeutic strategies, and shedding light on the crosstalk between proteinopathies and autophagy-lysosomal system defects. Eventually, emerging easily accessible biomarkers such as serum neurofilament light chains (NfL) might detect subclinical neurologic involvement in cystinosis patients.

Factors associated with D-lactic acidosis in pediatric intestinal failure: A case-control study.

D-lactic acidosis (DLA) is a serious complication of short bowel syndrome (SBS) in children with intestinal failure (IF). Malabsorbed carbohydrates are metabolized by bacteria in the intestine to D-lactate which can lead to metabolic acidosis and neurologic symptoms. A retrospective chart review was performed in children ≤18 years old with SBS who had one of the following criteria: unexplained metabolic acidosis, neurologic signs or symptoms, history of antibiotic therapy for small bowel bacterial overgrowth, or high clinical suspicion of DLA. Cases had serum D-lactate concentration >0.25 mmol/L; controls with concentrations ≤0.25 mmol/L. Of forty-six children, median age was 3.16 (interquartile range (IQR): 1.98, 5.82) years, and median residual bowel length was 40 (IQR: 25, 59) cm. There were 23 cases and 23 controls. Univariate analysis showed that cases had significantly lower median bicarbonate (19 vs. 24 mEq/L, p = 0.001), higher anion gap (17 vs. 14 mEq/L, p < 0.001) and were less likely to be receiving parenteral nutrition, compared with children without DLA. Multivariable analysis identified midgut volvulus, history of intestinal lengthening procedure, and anion gap as significant independent risk factors. Midgut volvulus was the strongest independent factor associated with DLA (adjusted odds ratio = 17.1, 95% CI: 2.21, 133, p = 0.007). DLA is an important complication of pediatric IF due to SBS. Patients with IF, particularly those with history of midgut volvulus, having undergone intestinal lengthening, or with anion gap acidosis, should be closely monitored for DLA.

Long-term quality of life and functional outcomes after management of spinal epidural abscess

BACKGROUND/CONTEXTIn recent years, the incidence of spinal epidural abscesses (SEA) has tripled in number and nonoperative management has risen in popularity. While there has been a shift towards reserving surgical intervention for patients with focal neurologic deficits, a third of patients will still fail medical management and require surgical intervention. Failure to understand long-term quality of life and functional outcomes hinders effective decision making and prognostication. PURPOSETo describe patterns and associated factors impacting long-term quality of life following treatment of spinal epidural abscess. STUDY DESIGN/SETTINGMulticenter cohort study at two urban academic tertiary referral centers and two community centers. PATIENT SAMPLEAdult patients treated for a spinal epidural abscess. OUTCOME MEASURESEuroQoL 5-Dimension 5L (EQ5D), Neuro-Quality of Life Lower Extremity – Mobility (Short Form; NeuroQoL-LE), Patient-Reported Outcomes Measurement Information System Physical Function (short form 4a; PROMIS PF), and PROMIS Global Mental Health score (PROMIS Mental). METHODSEligible patients were enrolled and administered questionnaires. Multivariable analysis assessed the influence of ambulatory status on HRQL, adjusting for covariates including age, biologic sex, Charlson comorbidity index, intravenous drug use, management approach, and ASIA grade on presentation. RESULTSSixty-one patients were enrolled (mean age 60.5 years, 46% male). Thirty-four patients (58%) underwent operative management. Mean standard deviation (SD) results for HRQL measures were: EQ5D 0.51 (0.37), EQ5D visual analogue scale 60.34 (25.11), NeuroQoL Lower extremity 41.47 (10.64), PROMIS physical function 39.49 (10.07), and PROMIS Global Mental Health 44.23 (10.36). Adjusted analysis demonstrated ambulatory status at presentation, and at 1 year, to be important drivers of HRQL, irrespective of other factors including IVDU and ASIA grade. Patients with independent ambulatory function at 1 year had mean EQ5D utility of 0.65 (95% CI 0.55, 0.75), whereas those requiring assistive devices saw a 49% decrease with mean EQ5D utility of 0.32 (0.14, 0.51). Ambulatory status was associated with global and physical function but did not impact overall health self-assessment or mental health scores. CONCLUSIONSWe found that ambulatory status was the most important factor associated with long-term HRQL regardless of other factors such as ASIA grade or IVDU. Given prior literature demonstrating the protective effect of operative intervention on ambulatory function, this highlights ambulatory dysfunction as a potential indication for surgery and a marker of poor long-term prognosis, even in the absence of focal neurologic deficits. Our work also highlights the importance of optimized long-term rehabilitation strategies aimed to preserve ambulatory function in this high-risk population. Level of EvidenceLevel III, cohort study

The Spontaneous Incidence of Neurological Clinical Signs in Preclinical Species Using Cage-side Observations or High-definition Video Monitoring: A Retrospective Analysis.

When conducting toxicology studies, the interpretation of drug-related neurological clinical signs such as convulsions, myoclonus/myoclonic jerks, tremors, ataxia, and salivation requires an understanding of the spontaneous incidence of those observations in commonly used laboratory animal species. The spontaneous incidence of central nervous system clinical signs in control animals from a single facility using cage-side observations or high definition video monitoring was retrospectively analyzed. Spontaneous convulsions were observed at low incidence in Beagle dogs and Sprague-Dawley rats but were not identified in cynomolgus monkeys and Göttingen minipigs. Spontaneous myoclonic jerks and muscle twitches were observed at low incidence in Beagle dogs, cynomolgus monkeys, and Sprague-Dawley rats but were not seen in Göttingen minipigs. Spontaneous ataxia/incoordination was identified in all species and generally with a higher incidence when using video monitoring. Salivation and tremors were the two most frequent spontaneous clinical signs and both were observed in all species. Data from the current study unveil potential limitations when using control data obtained from a single study for toxicology interpretation related to low incidence neurological clinical signs while providing historical control data from Beagle dogs, cynomolgus monkeys, Sprague-Dawley rats, and Göttingen minipigs.

Childhood stroke: A prospective study on risk factors, clinical profile, and short-term outcome in a tertiary care hospital in Eastern India

Background: Childhood stroke is an acute onset neurological sign or symptom attributable to focal brain infarction or haemorrhage. It is an under-studied entity and is scarcely reported from India.Objectives: To evaluate the risk factors, clinical profile and short-term outcome (after a 6-month follow-up) of childhood stroke in a tertiary care hospital of Eastern India.Method: This observational, prospective study was conducted on 50 patients aged 2 months to 12 years over a period of 18 months. Data on history, examination, relevant investigations, radio-imaging and follow-up was taken and recorded on a pre-formed proforma and analysed.Results: Out of the 50 cases, 23 (46%) had arterial ischaemic stroke (AIS), 12 (24%) had cerebral sino-venous thrombosis (CSVT) and 15 (30%) had haemorrhagic stroke (HS). The common risk factors were infection (30%) and vascular disorder (24%), including arteriopathy and vascular malformation. Common presentations were seizures (78%) and hemiparesis (70%). Eight (16%) cases died. Although none died among AIS and CSVT cases, there was statistically significant mortality in HS (p&lt;0.001). After 6-month follow-up of discharged cases (n=42), partial neurological recovery was noted in 64.3%.Conclusions: AIS was the most common type of stroke. Commonest risk factor was infection and commonest presentation was seizure. Mortality was observed only in HS. Majority achieved partial neurological recovery on short-term follow-up.

Meningoencefalomielite por Cryptococcus spp. em felino

Cryptococcosis is a systemic mycosis caused by encapsulated yeasts from the gender Cryptococcus. It mainly affects the nasal cavity, adjacent tissue and lungs, and can spread to the central nervous system, eyes and skin, causing meningoencephalomyelitis. It can be noninfectious or infectious via yeasts and bacteria, and felines are the most prevalent when infected by the Feline Leukemia Virus (FeLV) or Feline Infectious Peritonits (FIP). The neurological signs of infection by criptococcus could be convulsion, depression, disorientation, ataxia, paralysis of the pelvic limbs, mydriasis and blindness. For diagnosis, the neurological exam is indispensable, and must be combined with the general full body physical exam, with the intention to find the injury. The aim of this study is to report the case of a cat, 10 months old, with meningoencephalomyelitis by Cryptococcus spp. The animal presented the clinical signs of abrupt change in behavior, excessive fear, lack of appetite and progressive weight loss. Methadone was administrated for the pain, used gabapentin that changed for pregabalin. Cerebrospinal fluid (CSF) analysis and MRI were performed to assist in the diagnosis. However, false negatives can occur, which may consequently hinder adequate treatment. In this report, diagnostic conclusion occurred post-mortem. Thus, the patient lacked the adequate treatment to stabilize in life.

Outcomes of thrombotic thrombocytopenic purpura patients submitted to therapeutic plasma exchange in a single center in Brazil

IntroductionImmune thrombotic thrombocytopenic purpura (iTTP) is characterized by acute systemic microvascular thrombosis and is associated with a high morbidity and mortality, especially in delayed diagnosis (later than 6–7 days from symptoms). iTTP data in Brazil is scarce, so we aimed to characterize the clinical presentation and identify predictors of death risk in patients with this disease in Brazil. MethodsIn this single-center retrospective study the patients who underwent therapeutic plasma exchange (TPE) for presumptive or confirmed iTTP were evaluated regarding the epidemiological, clinical, laboratorial characteristics and management. ResultsA total of 50 patients (90 % female), with median age (IQR) of 34.1 (27–47) years, were enrolled, of which 12 (24 %) died. The most frequent symptoms were neurological (96 %), bleeding (76 %), gastrointestinal (52 %), fever (38 %), and cardiovascular (22 %). Neurological focal deficit and cardiovascular symptoms were more frequently observed in the non-survivor group (P = 0.0019 and P = 0.007, respectively). The mean ± SD number of days from beginning of symptoms to first TPE was 12.22 ± 7.91. We identified an association regarding mortality rate with a score MITS ≥ 2 points (P = 0.04), a higher indirect bilirubin (P = 0.0006), a higher number of transfused red blood cell units (P = 0.025), and platelet transfusion (P = 0.027). ConclusionDelayed diagnosis appears to be associated with a higher frequency of neurological symptoms and mortality. Intensity of hemolysis and signs of organ ischemia, such as cardiovascular symptoms and focal neurological deficit, are indicators of death risk.

Neurologic Complications of Cancer Immunotherapy.

Immunotherapeutic approaches have revolutionized cancer treatment with immune checkpoint inhibitors and adoptive T-cell therapy now approved to treat a variety of solid and hematologic malignancies. This article summarizes the distinctive neurologic side effects of these therapies as well as their management. Neurologic immune-related adverse events are rare but potentially serious complications of immune checkpoint inhibitors. Both peripheral and central nervous system disorders have been described, often necessitating a pause or cessation of immunotherapy. Immune effector cell-associated neurotoxicity syndrome is a potentially serious complication of chimeric antigen receptor T-cell therapy. While symptoms may be mild and self-limited, delirium, encephalopathy, seizures, focal neurologic deficits, and fulminant cerebral edema can be seen. Close neurologic monitoring is imperative. The mainstay of treatment for neurologic complications includes high-dose corticosteroids, although other immunomodulatory strategies may be used in severe or refractory cases. The spectrum of neurologic complications of cancer immunotherapy is broad, encompassing both central and peripheral nervous system disorders, indolent as well as fulminant clinical presentations, and wide-ranging severity with variable response to treatment. Early identification and multidisciplinary management are crucial to balance neurologic recovery and antitumor control.

Clinical Manifestations.

The Hachinski ischemic score (HIS) scale is used to exclude as much as possible, individuals with dominant cerebrovascular pathology from those with dominant AD pathology. White matter hyperintensities (WMH) are the gold-standard for evaluating cerebrovascular pathology and linked to worsening cognitive impairment. HIS ≤ 4 are used to minimize non-AD pathology in ADNI participants. Here we sought to understand whether HIS scores for hypertension (HMHYPERT) in ADNI3 were associated with greater WMH burden (and hence cerebrovascular pathology) even within individuals with HIS ≤ 4. We compared HMHYPERT scores between individuals with normal cognition (CN) and with mild cognitive impairment (MCI), and participants and correlated with percent WMH burden. A total of 263 subjects screened for ADNI3 (92 MCI [38 F], age = 73 ± 6; 146 CN [94 F], age = 74 ± 7) who had HIS scores and FLAIR MRI acquisitions within a year of each other. 25 All AD participants were excluded. WMH burden was calculated by segmenting them using the Lesion Segmentation Toolbox and normalizing their volume by total intracranial volume. We used the HMHYPERT as a vascular risk factor, excluding those with any focal neurological symptoms. For analysis, we dichotomized participants into those with HMHYPERT = 0 and HMHYPERT>0. To examine whether a non-zero HMHYPERT score corresponds to greater WMH burden, we examined the prevalence of WMH in between these 2 groups and within the MCI and CN groups. Although not significant, HMHYPERT scores were higher in MCI. (Fig. 1A, MCI = 0.48±0.50, CN = 0.39±0.49). We found a greater proportion of MCI subjects had HMHYPERT>0 than CN subjects (Fig. 1B, HMHYPERT = 0: CN = 61.0% and MCI = 52.2%; HMHYPERT > 0: CN = 40.0% and MCI = 48.1%). WMH burden was greater in MCI (0.33±0.53) than CN (0.20±0.32) (Fig. 2A). MCI participants with HMHYPERT>0 had the highest WMH burden followed by MCI participants with HMHYPERT = 0, CN with HMHYPERT >0, and CN with HMHYPERT = 0 had the lowest WMH burden. (Fig. 2B). Cerebrovascular pathology increases significantly with diagnosis, but its severity increases further with findings of hypertension even when total HIS ≤ 4.

Clinical Manifestations.

In recent years, there has been an increase in the number of case reports of families with autosomal dominant Alzheimer's disease (ADAD) in Latin America (LA). Nevertheless, little is known about the clinical phenotypes and demographic characteristics of mutations in each country. Past literature has proved that variants in LA have different and unique characteristics than those reported in Asia, North America, and Europe. Clinical heterogeneity in ADAD supports the need to study clinical phenotypes, especially in preclinical stages, to develop cognitive and clinical markers of the disease. We aimed to describe clinical and cognitive characteristics at baseline assessment of an Argentina PSEN1 p.M146L family enrolled at DIAN. Fifteen Dian Participants living in Buenos Aires and its suburbs and in Taco Pozo, a rural and isolated community from the Province of Salta, positive for the PSEN1 p.M146L mutation, were recruited. DNA was obtained from peripheral blood leukocytes according to standard protocols. In addition, exon 5 of the PSEN1 gene was PCR-amplified, and Sanger sequencing was performed. NACC Uniform Data Set clinical assessment, including the 2.0 UDS Neuropsychological Battery, was administered. Two groups were used to compare cognitive data: Patients with CDR:0 (n:10) and patients with CDR>0 (n:5). The mean age at symptom onset reported in this cohort was 42,90 (SD: 4,62). Significant differences were found in several cognitive measures: Logical Memory Immediate, TMT B and Digit Backward (<0,001); MMSE, Category Fluency Animals, TMT A and Digit Symbol(<0,05). In neurological signs, paraplegia was reported in one of the patients. As expected, differences in neuropsychological tests showed a prevalence of memory deficits, however, dysexecutive symptoms were also present for this mutation. Paraplegia in PSEN1 p.M146L has not been reported in the literature so far. Ongoing longitudinal work will be important in tracking changes in this cohort. Other characteristics, proper of underrepresented groups, such as socioeconomic status, education, race, and ethnicity, deserve appropriate follow-up. Future studies are planned, comparing urban and rural populations in this cohort with the same mutation.

Neurological disease in xeroderma pigmentosum: prospective cohort study of its features and progression.

Xeroderma pigmentosum (XP) results from biallelic mutations in any of eight genes involved in DNA repair systems, thus defining eight different genotypes (XPA, XPB, XPC, XPD, XPE, XPF, XPG and XP variant or XPV). In addition to cutaneous and ophthalmological features, some patients present with XP neurological disease. It is unknown whether the different neurological signs and their progression differ among groups. Therefore, we aim to characterize the XP neurological disease and its evolution in the heterogeneous UK XP cohort. Patients with XP were followed in the UK National XP Service, from 2009 to 2021. Age of onset for different events was recorded. Cerebellar ataxia and additional neurological signs and symptoms were rated with the Scale for the Assessment and Rating of Ataxia (SARA), the Inventory of Non-Ataxia Signs (INAS) and the Activities of Daily Living questionnaire (ADL). Patients' mutations received scores based on their predicted effects. Data from available ancillary tests were collected. Ninety-three XP patients were recruited. Thirty-six (38.7%) reported neurological symptoms, especially in the XPA, XPD and XPG groups, with early-onset and late-onset forms, and typically appearing after cutaneous and ophthalmological symptoms. XPA, XPD and XPG patients showed higher SARA scores compared to XPC, XPE and XPV. SARA total scores significantly increased over time in XPD (0.91 points/year, 95% confidence interval: 0.61, 1.21) and XPA (0.63 points/year, 95% confidence interval: 0.38, 0.89). Hyporeflexia, hypopallesthaesia, upper motor neuron signs, chorea, dystonia, oculomotor signs and cognitive impairment were frequent findings in XPA, XPD and XPG. Cerebellar and global brain atrophy, axonal sensory and sensorimotor neuropathies, and sensorineural hearing loss were common findings in patients. Some XPC, XPE and XPV cases presented with abnormalities on examination and/or ancillary tests, suggesting underlying neurological involvement. More severe mutations were associated with a faster progression in SARA total score in XPA (0.40 points/year per 1-unit increase in severity score) and XPD (0.60 points/year per 1-unit increase), and in ADL total score in XPA (0.35 points/year per 1-unit increase). Symptomatic and asymptomatic forms of neurological disease are frequent in XP patients, and neurological symptoms can be an important cause of disability. Typically, the neurological disease will be preceded by cutaneous and ophthalmological features, and these should be actively searched in patients with idiopathic late-onset neurological syndromes. Scales assessing cerebellar function, especially walking and speech, and disability can show progression in some of the groups. Mutation severity can be used as a prognostic biomarker for stratification purposes in clinical trials.

Cumulative seizure occurrence and the predictors of seizure in low- and high-grade gliomas

Objective: We aimed to determine the cumulative seizure occurrence, 1-year, and 5-years of preoperative seizures in gliomas, and an update on the predictors. Methods: This was a retrospective analysis of 239 patients with histopathologically confirmed gliomas in University Malaya Medical Centre, Malaysia, between 2008-2020. Kaplan-Meier curves were used to determine the cumulative incidence of seizures. Logistic regression was performed to determine the predictors of preoperative seizures. Results: A total of 80/239 patients (33.5%) had preoperative seizures. They were more commonly seen in those with younger age of presentation (40.0% in those &lt;40 years old vs. 26.9% in ≥40 years old, p&lt;0.05) and low-grade tumors (42.2% vs. 28.8% in high-grade tumors). Those with cortical involvement, especially the frontal lobe, or without focal deficit, headache, nausea, or vomiting were more likely to have seizures preoperatively. Logistic regression identified three significant predictors for preoperative seizure: absence of focal deficits at presentation (OR 6.090, 95% CI 3.110-11.925, p&lt;0.001), cortical location (OR 3.834, 95% CI 1.363-10.786, p&lt;0.05) and absence of headache at presentation (OR 2.487, 95% CI 1.139-5.431, p&lt;0.05). The cumulative incidence of seizure was 29% at one year and 32% at 5-year for gliomas. Specifically, the seizure incidence was higher in low-grade gliomas (39% at 1-year) and certain tumor types such as ganglioglioma (50%), oligodendroglioma (48%), and astrocytoma (45%). Conclusion: The cumulative incidence of preoperative seizures in low-grade gliomas and certain tumor types is high. The predictors included cortical involvement and absence of focal neurological deficit or headache at presentation.