Subacute Cognitive Impairment Research Articles

Characteristics and prognosis of LGI1 antibody encephalitis

Objectives: To investigate clinical manifestations and outcomes of patients with LGI1 autoimmune encephalitis. Methods: A total of 12 patients who were diagnosed with LGI1 autoimmune encephalitis were retrospectively analyzed between 2018 and 2022 at the Department of Neurology of the Affiliated Hospital of Xuzhou Medical University. Clinical characteristics, laboratory examinations, electroencephalograms, brain magnetic resonance images and prognosis were assessed. The clinical data were collected by searching through electronic medical records. Results: Among 12 patients, 8 were male and 4 were female. The average age at disease onset was 61.8 years (24–83). The most common clinical symptoms were seizures (n=10), cognitive dysfunction (n=8), and mental behavioral disorders (n=8). A total of 9 cases had hyponatremia. Brain MRI and electroencephalographic were abnormal in 7 patients each. All patients were treated with first line immunotherapy. Most patients responded well and 3 patients relapsed on follow-up. Conclusion: Characteristic features of LGI1 antibody encephalitis include subacute onset cognitive impairment, seizures, faciobrachial dystonic seizures (FBDS), and mental and behavioral abnormalities. Especially, FBDS and hyponatremia suggest LGI1-antibody encephalitis. Therefore, early identification and immunotherapy may prevent cognitive impairment and improve prognosis.

Altered neural recruitment despite dual task performance recovery in athletes with repeat concussion.

Sports-related concussions (SRCs) pose significant challenges to college-aged athletes, eliciting both immediate symptoms and subacute cognitive and motor function impairment. While most symptoms and impairments resolve within weeks, athletes with repeat SRCs may experience heightened risk for prolonged recovery trajectories, future musculoskeletal injuries, and long-term neurocognitive deficits. This includes impaired dual task performance and altered neurophysiology that could persist across the lifespan and elicit future pathophysiology and neurodegeneration. Thus, it is imperative to improve our understanding of neurophysiology after SRC. This study aimed to investigate the impact of repeat SRCs on dual task performance and associated neural recruitment using functional near-infrared spectroscopy (fNIRS). A total of 37 college-aged athletes (ages 18-24) participated in this cross-sectional observational study. Among these athletes, 20 had a history of two or more SRCs, while 17 had never sustained a SRC and served as controls. Participants completed the Neuroimaging-Compatible Dual Task Screen (NC-DTS) while fNIRS measured neural recruitment in the frontoparietal attention network and the primary motor and sensory cortices. Behavioral analysis revealed that athletes with repeat SRCs exhibited comparable single task and dual task performance to control athletes. Additionally, dual task effects (DTE), which capture performance declines in dual tasks versus single tasks, did not significantly differ between groups. Notably, the cohort of athletes with repeat SRC in this study had a longer time since their last SRC (mean = 1.75 years) than majority of previous SRC studies. Neuroimaging results indicated altered neural recruitment patterns in athletes with multiple repeat SRCs during both single and dual tasks. Specifically, athletes with repeat SRCs demonstrated increased prefrontal cortex (PFC) activation during single motor tasks compared to controls (P < 0.001, d = 0.47). Conversely, during dual tasks, these same athletes exhibited reduced PFC activation (P < 0.001, d = 0.29) and primary motor cortex (M1) activation (P = 0.038, d = 0.16) compared to their single task activation. These findings emphasize the complex relationship between SRC history, dual task performance, and changes in neurophysiology. While athletes with repeat SRCs demonstrate recovery in behavioral dual task performance, persistent alterations in neural recruitment patterns suggest ongoing neurophysiological changes, possibly indicating compensatory neural strategies and inefficient neural resource allocation, even beyond symptom resolution and medical clearance. Understanding the compensatory neural recruitment strategies that support behavioral performance following repeat SRCs can inform return-to-play decisions, future musculoskeletal injury risk, and the long-term impact of SRCs on neurocognitive function.

A rare disease with atypical clinical and imaging findings: Anti LGI-1 encephalitis

Anti-leucine-richglioma inactivated protein 1 (LGI1) encephalitis is of autoimmune origin, characterized by subacute cognitive impairment and faciobrachial dystonic seizures. We present a case that will raise awareness about the disease with atypical clinical and rich imaging findings that has benefited greatly from intensive immunotherapy despite its poor prognosis.

Subacute cognitive impairment as clinical presentation of primary angiitis of the central nervous system

Subacute cognitive impairment as clinical presentation of primary angiitis of the central nervous system

Antibody-LGI 1 autoimmune encephalitis manifesting as rapidly progressive dementia and hyponatremia: a case report and literature review

BackgroundAnti leucine-rich glioma inactivated 1 (LGI1) encephalitis is a rare autoimmune encephalitis (AE), characterized by acute or subacute cognitive impairment, faciobrachial dystonic seizures, psychiatric disturbances and hyponatremia. Antibody-LGI 1 autoimmune encephalitis (anti-LGI1 AE) has increasingly been recognized as a primary autoimmune disorder with favorable prognosis and response to treatment.Case presentationHerein, we reported a male patient presenting as rapidly progressive dementia and hyponatremia. He had antibodies targeting LGI1 both in the cerebrospinal fluid and serum, which demonstrated the diagnosis of typical anti-LGI1 AE. The scores of Mini-Mental State Examination and Montreal Cognitive Assessment were 19/30 and 15/30, respectively. Cranial magnetic resonance images indicated hyperintensities in bilateral hippocampus. The findings of brain arterial spin labeling and Fluorine-18-fluorodeoxyglucose positron emission tomography showed no abnormal perfusion/metabolism. After the combined treatment of intravenous immunoglobulin and glucocorticoid, the patient’s clinical symptoms improved obviously.ConclusionsThis case raises the awareness that a rapid progressive dementia with predominant memory deficits could be induced by immunoreactions against LGI1. The better recognition will be great importance for the early diagnosis, essential treatment, even a better prognosis.

Autoimmune encephalitis. A review

Autoimmune encephalitis are one of the emergent causes of subacute changes in the level of consciousness, behavior, cognitive impairment and seizures, mainly in young people. They are a consequence of inflammation or dysfunction of parts of the brain caused by antibodies against specific brain antigens, usually located in the limbic system, resulting in clinical presentation as a limbic encephalitis. The objectives of this article are to show the clinical presentation, complementary studies and treatment of this entity, considering that the patient's prognostic depends on a high level of clinical suspicion, and on an early initiation of immunosuppressive therapy. We did a nonsystematic review of the literature on autoimmune encephalitis between 2005 and 2017. We conclude that the prevalence of autoimmune encephalitis is increasing, even surpassing infectious causes of encephalitis in developed countries. Clinical presentation includes sub-acute cognitive and behavioral impairment, with or without alterations in consciousness and seizures. Fever and inflammation of the cerebrospinal fluid are less common than in the infectious causes but psychiatric symptoms are more frequent. There are specific clinical presentations according to the particular type of antigen/antibody present, which also determines the association with cancer, constituting a paraneoplastic syndrome only in some cases. Immunosuppressive therapy has been standardized in steps, and should be initiated early to improve prognosis.

Adrenoleucodistrofia ligada al X con patrón radiológico atípico

X-linked adrenoleukodystrophy (X-ALD) is the most frequent peroxisomal disease. It is due to a mutation in the ABCD1 gene. The loss of functioning of ABCD1 triggers ineffective beta oxidation of very long-chain fatty acids, which gives rise to an accumulation of these fatty acids. The typical alteration revealed in neuroimaging scans in the cerebral form is symmetrical periventricular demyelination with posterior location. We report the case of a 10-year-old boy with right spastic hemiparesis and subacute cognitive impairment. Magnetic resonance imaging of the brain showed symmetrical involvement of the white matter in the left frontoparietotemporal region, and calcifications were observed in the computerised axial tomography scan. X-ALD was confirmed by means of the elevated levels of very long-chain fatty acids, and a pathogenic variant was found in the ABCD1 gene. Symmetrical demyelination with calcifications has rarely been reported in X-ALD, and these findings could delay diagnosis. This exceptional presentation should always be taken into consideration in children with subacute onset of motor symptoms and cognitive or behavioural regression.

How Long Should Routine EEG Be Recorded to Get Relevant Information?

The optimal duration of routine EEG (rEEG) has not been determined on a clinical basis. This study aims to determine the time required to obtain relevant information during rEEG with respect to the clinical request. All rEEGs performed over 3 months in unselected patients older than 14 years in an academic hospital were analyzed retrospectively. The latency required to obtain relevant information was determined for each rEEG by 2 independent readers blinded to the clinical data. EEG final diagnoses and latencies were analyzed with respect to the main clinical requests: subacute cognitive impairment, spells, transient focal neurologic manifestation or patients referred by epileptologists. From 430 rEEGs performed in the targeted period, 364 were analyzed: 92% of the pathological rEEGs were provided within the first 10 minutes of recording. Slowing background activity was diagnosed from the beginning, whereas interictal epileptiform discharges were recorded over time. Moreover, the time elapsed to demonstrate a pattern differed significantly in the clinical groups: in patients with subacute cognitive impairment, EEG abnormalities appeared within the first 10 minutes, whereas in the other groups, data could be provided over time. Patients with subacute cognitive impairment differed from those in the other groups significantly in the elapsed time required to obtain relevant information during rEEG, suggesting that 10-minute EEG recordings could be sufficient, arguing in favor of individualized rEEG. However, this conclusion does not apply to intensive care unit patients.

Clinical analysis of 22 cases with Hashimoto's encephalopathy

Objective To investigate the clinical presentations of Hashimoto's encephalopathy (HE), so as to improve the diagnosis and treatment of this disease. Methods A retrospective analysis was performed on clinical features, laboratory findings, imaging profiles, treatment and outcomes of 22 patients with HE who were admitted to our hospital between June 2010 and September 2013. Results Clinical symptoms were mainly acute or subacute cognitive impairment (9 cases), psychiatric symptoms (6 cases), seizures (5 cases), ataxia (5 cases), stroke-like episodes (6 cases), tremor (1 case), myoclonus (2 cases) and disturbance of consciousness (3 cases). Marked increase was found in serum anti-thyroid peroxidase (anti-TPO) antibody level (19 cases) and anti-thyroglobulin (anti-TG) antibody level (20 cases). Twenty-one cases were treated with glucocorticoids, and one patient was treated only with general neurotrophic therapy, such as ganglioside. Except for 4 cases showed bad response to steroids, the rest patients had an obvious improvement. Conclusions Hashimoto's encephalopathy is an encephalopathy with the presence of elevated antithyroid antibodies, and most patients showed good response to steroids. So early diagnosis and treatment is particularly important for improving prognosis. This disease should be considered as an important differential diagnosis for encephalopathy of unknown etiology, and screening for serum antithyroid antibodies should be performed as initial screening test. doi: 10.3969/j.issn.1672-6731.2014.07.008

Paraneoplastic limbic encephalitis with prominent neuropsychiatric apathy

The spectrum of paraneoplastic neurologic syndromes has increased with the description of encephalitis associated with antibodies against cell surface and synaptic proteins. Subacute cognitive impairment, movement disorders, late onset epilepsy and neuropsychiatric syndromes were recently linked to paraneoplastic encephalitis. Despite that, probably some syndromes and antibodies are yet to be reported. Herein we reported the clinical and neuroimaging pictures of a patient with late onset medial temporal lobe epilepsy, subtle cognitive impairment, psychosis and severe apathy diagnosed with antibody-negative paraneoplastic encephalitis due to colonic adenocarcinoma. The apathy markedly improved after removal of the tumor, without concomitant immunotherapy (steroids, intravenous immunoglobulins, immunosuppressants, plasmapheresis, etc.). Our report highlights the importance of a full clinical and neurologic investigation in cases of atypical neuropsychiatric presentations, particularly in the elderly and with the concomitance of epilepsy and cognitive decline. Even chronic presentations must be considered. Neuroimaging is an important tool to demonstrate structural and functional brain dysfunction in these cases. Colonic adenocarcinoma should be searched for in cases in which a typical tumor related to paraneoplastic neurologic syndromes is not found.

P16 The effects of treating VGKC associated limbic encephalitis in the elderly: a systematic review

Background In the elderly, a decline in cognitive function is often associated with dementia. However, subacute deterioration on memory functions, associated with affective change and/or seizures are also classical features of limbic encephalitis, which is caused by inflammation of the limbic areas of the brain. Paraneoplastic limbic encephalitis is caused by the production of autoantibodies against neuronal tissues secondary to certain cancers. Similar autoantibodies have also been noted in the absence of neoplasms in non-paraneoplastic limbic encephalitis (nPLE), commonly reported antibodies being produced against Voltage Gated Potassium Channels (VGKC), which results in neuropsychiatric symptoms. This study aims to systematically review the evidence of the effects of treating VGKC associated limbic encephalitis in the elderly with intravenous Immunoglobulins, plasma exchange or steroids. Method A systematic review of the available published and unpublished data were conducted, using the MEDLINE, EMBASE and PsychINFO databases, using pre-defined inclusion and exclusion criteria. Information such as patient demographics, presenting symptoms, treatment and antibody levels were gathered using a standardised data collection tool. The results were statistically analysed for correlation between clinical outcome and antibody titres before and after treatment. Results A total of 59 cases met the inclusion criteria of whom 50 cases had complete data for statistical analysis. Twenty-one cases were over the age of 65 with complete data sets. Patients who clinically improved had the largest decrease in antibody titres. Patients presenting with affective and consistent neuroradiological changes were more likely to have an improved outcome following treatment. These results proved to be statistically significant. Statistical analysis also showed that 67.6% of patients below the age of 65 had an MRI change compared to 80% of patients above the age of 65. However, the observation was not statistically significant (p=0.292 χ2 test). Conclusion The overall evidence suggests that treatment of VGKC associated nPLE is effective. There are currently no agreed diagnostic guidelines, validated assessment tools or randomised controlled trials of the different treatment options. nPLE is a treatable condition which should form part of the differential diagnosis when patients present with subacute cognitive impairment, associated with affective changes and seizures.

Encefalopatía reversible por ácido valproico en un adolescente con epilepsia generalizada idiopática

Encephalopathy due to valproic acid (VPA) is a rare complication leading to a disorder that affects the patient's mental status to a greater or lesser extent and which can be accompanied by a paradoxical worsening of the seizures. The diagnosis is obvious when it appears within the context of hyperammonemia or a liver pathology, but can be difficult to diagnose if it appears in isolation in patients who show no other signs of intoxication due to VPA. We report the case of an adolescent who suffered idiopathic generalised epilepsy and presented sub-acute cognitive impairment and a worsening of his pattern of seizures some months after starting treatment with VPA. These manifestations were accompanied by a slowing of the baseline electroencephalogram (EEG) tracing; no biochemical signs of overdosage or toxicity that could be attributed to the drug or any other possible aetiology were observed. Withdrawing VPA resulted in a swift improvement in the patient's mental status and in the control of his seizures. Likewise, EEG recordings also returned to normal. Encephalopathy due to VPA should be considered in patients who present a deterioration of their neurological status, whether associated to an aggravation of their seizures or not, despite the absence of any analytical signs suggestive of VPA toxicity or overdosage. If liver functioning is not affected, withdrawal of the drug will determine the disappearance of the symptoms and will also allow confirmation of the diagnosis.

Subacute cognitive impairment, hyponatremia and mesial temporal lobe lesions: a typical presentation of voltage-gated potassium channel (VGKC) antibody-associated limbic encephalitis

. Herein, we present a case of VGKC antibody-asso-ciated LE and discuss the main phenotypic and imaging features of this unusual disease.CASE A 50-year-old man presented to our hospital with three months history of progressive personality change, sleep disturbance, memory impairment, visual halluci-nations and seizures. Neurological examination showed disorientation, cognitive impairment (Mini Mental State Examination: 13) and memory dysfunction. Blood tests showed hyponatremia - 130 mmol/L (135-145 mmol/L). Thyroid function, antibodies and serologic tests were normal. Cerebrospinal fluid showed high level of pro-teins (558 mg/dL) and mild lymphocytic pleocytosis. Brain magnetic resonance imaging (MRI) disclosed bi-lateral T2 and FLAIR hyperintensity of mesial temporal lobes (Figure). Cancer investigation resulted negative. VGKC serum level was higher than 650 pmol/L (normal range less than 450 pmol/L). These findings confirmed the diagnosis LE with VGKC antibodies. Methylpred-nisolone was started, with partial improvement. Three weeks later, immunoglobulin 0.4 g/Kg daily for five con-secutive days was initiated. One week after immunoglob-

Utility of measuring vitamin B12 and its active fraction, holotranscobalamin, in neurological vitamin B12 deficiency syndromes

Vitamin B(12) (VitB(12), cobalamin) deficiency has been associated with various neuropsychiatric conditions, such as peripheral neuropathy, subacute combined degeneration, affective disorders, and cognitive impairment. Current assays analyze vitamin B(12), of which only a small percentage is metabolically active. Measurement of its active fraction, holotranscobalamin, might be of greater relevance, but data in populations with neuropsychiatric populations are lacking. In this study, in order to validate VitB(12) and holotranscobalamin (holoTC) serum levels for the detection of VitB(12) deficiency in neuropsychiatric conditions, we compared the validity of VitB(12) and holoTC in a patient cohort with neuropsychiatric conditions suspicious for VitB(12) deficiency. The cohort included all patients admitted to the Department of Neurology at our university between 2005 and 2009 with at least two parameters of the VitB(12) metabolism available (n = 1,279). We used elevated methylmalonic acid as the external validation criterion for VitB(12) deficiency and restricted our analyses to subjects with normal renal function. Among all normal renal function patients, 13.2% had VitB(12) deficiency. In receiver operating characteristic curve (ROC) analysis, correlation of VitB(12) and holoTC with vitamin B(12) deficiency was generally weak, and the areas under the curve (AUC) were not significantly different for holoTC compared to vitamin B(12) in all subjects (AUC: 0.66 [95%CI: 0.51-0.82]; p = 0.04 vs. 0.72 [0.65-0.78], p < 0.0001) and in subcohorts of patients with classical VitB(12) deficiency syndromes. The positive predictive values for holoTC and vitamin B(12) were low (14.7 vs. 21.0%) and both were associated with more false-positive than true-positive test results. holoTC does not show superior diagnostic accuracy compared to VitB(12) for the detection of VitB(12) deficiency in subjects with neuropsychiatric conditions. Neither test can be recommended to diagnose VitB(12) deficiency in subjects with neuropsychiatric disorders.

Hashimoto's Encephalopathy with Selective Involvement of the Nucleus Accumbens: A Case Report

Hashimoto's encephalopathy (HE) is an acute or subacute relapsing disorder usually affecting euthyroid patients with evidence of autoimmune thyroiditis. The neurological manifestations are non-specific, with subacute cognitive impairment, movement disorders, generalized seizures, focal neurological symptoms such as stroke-like episodes, or psychiatric disturbances. Autoimmune phenomena are likely to play an etiological role. Magnetic resonance imaging (MRI) findings are usually normal or show non-specific changes. We report the case of an 11-year-old girl with autoimmune thyroiditis who presented acutely with a complex neuropsychiatric disorder in association with MRI evidence of focal involvement of the nucleus accumbens (NA). The NA, a ventral striate nucleus, is part of a complex dopaminergic network. Lesions to the NA result in several psychiatric symptoms, such as attention-deficit hyperactivity disorders. In this patient, we observed alternating phases of stupor and hyperkinetic-anxious behavior, with marked instability. The pathogenetic mechanism and the anatomic and functional correlations are briefly discussed.

Quistes subaracnoideos gigantes por neurocisticercosis: a propósito de dos casos observados en un área rural de Extremadura

Neurocysticercosis is the commonest cerebral parasitosis. The most recent cases reported in Spain have occurred in patients from endemic countries. The formation of giant subarachnoid cysts (GSC) is an uncommon complication of neurocysticercosis and its treatment is the subject of debate. We report two cases seen recently in the Valle del Jerte, a rural district in Extremadura. Case 1. A 64 year old man had had complex partial crises (CPC) since 1985. In 1987 he was diagnosed as having neurocysticercosis with parenchymatous cysts and treated with praziquantel. In 1996, on CAT and MR a left frontal GSC was diagnosed and also two parenchymatous active cysts. The cyst was removed surgically and he was subsequently treated with albendazol. Case 2. A 72 year old man had generalized crises and CPC since 1970. In 1987 and 1991 on CAT and MR several parenchymatous lesions compatible with neurocysticercosis were seen. In 1997 he presented with headache and subacute cognitive impairment. On CAT and MR a left temporal GSC was seen with several active parenchymatous lesions. The patient was treated with albendazol and dexamethasone. Both patients improved, although radiological resolution of the GSC in case 2 took a year. Neurocysticercosis is a condition still present in Spain. GSC respond to treatment with albendazol, whilst surgical treatment is the best option when severe intracranial hypertension occurs.

Leukoencephalopathy associated with cobalamin deficiency

Patients with cobalamin deficiency may experience cognitive impairment or neuropsychiatric symptoms. Although abnormalities of central myelin are the presumed cause of these manifestations, there is a paucity of reports of white matter lesions as shown on neuroimaging studies, and the effects of cobalamin replacement on these lesions are not known. We report a man with subacute cognitive impairment associated with cobalamin deficiency and remarkable confluent white matter abnormalities on MRI, confirmed by biopsy. With cobalamin replacement, both his cognitive deficits and imaging abnormalities partially resolved. This case indicates that leukoencephalopathy, in the absence of anemia or myelopathy, should be added to the spectrum of disorders associated with cobalamin deficiency. Early detection and treatment may be associated with a greater potential for recovery.