Autoimmune Encephalitis in Late-Onset Seizures: When to Suspect and How to Treat

Objective: This study was conducted to elucidate prevalence, clinical features, outcomes, and best treatment in patients with late-onset seizures due to autoimmune encephalitis (AE).Methods: This is a single-institution prospective cohort study (2012–2019) conducted at the Epilepsy Center at the University of Greifswald, Germany. A total of 225 patients aged ≥50 years with epileptic seizures were enrolled and underwent an MRI/CT scan, profiling of neural antibodies (AB) in serum and cerebrospinal fluid (CSF), and neuropsychological testing. On the basis of their work-up, patients were categorized into the following three cohorts: definite, suspected, or no AE. Patients with definite and suspected AE were subsequently treated with immunosuppressive therapy (IT) and/or anti-seizure drug (ASD) therapy and were followed up (FU) regarding clinical and seizure outcome.Results: Of the 225 patients, 17 (8%) fulfilled the criteria for definite or suspected AE according to their AB profile and MRI results. Compared with patients with no evidence of AE, those with AE were younger (p = 0.028), had mesial temporal neuropsychological deficits (p = 0.001), frequently had an active or known malignancy (p = 0.006) and/or a pleocytosis (p = 0.0002), and/or had oligoclonal bands in CSF (p = 0.001). All patients with follow-up became seizure-free with at least one ASD. The Modified Rankin scale (mRS) at hospital admission was low for patients with AE (71% with mRS ≤2) and further decreased to 60% with mRS ≤2 at last FU.Significance: AE is an important etiology in late-onset seizures, and seizures may be the first symptom of AE. Outcome in non-paraneoplastic AE was favorable with ASD and IT. AB testing in CSF and sera, cerebral MRI, CSF analysis, and neuropsychological testing for mesial temporal deficits should be part of the diagnostic protocol for AE following late-onset seizures.

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K Index is a Reliable Marker of Intrathecal Synthesis, and an Alternative to IgG Index in Multiple Sclerosis Diagnostic Work-Up

Journal of Clinical Medicine ◽

10.3390/jcm8040446 ◽

2019 ◽

Vol 8 (4) ◽

pp. 446 ◽

Cited By ~ 4

Author(s):

Ilaria Crespi ◽

Domizia Vecchio ◽

Roberto Serino ◽

Elena Saliva ◽

Eleonora Virgilio ◽

...

Keyword(s):

Multiple Sclerosis ◽

Oligoclonal Bands ◽

Intrathecal Synthesis ◽

Csf Analysis ◽

K Index ◽

Igg Index ◽

Reliable Marker ◽

Diagnostic Work ◽

Work Up ◽

Diagnostic Work Up

The K free light chain (K) index has been suggested as a reliable marker of intrathecal synthesis,despite the 2017 McDonald criteria for multiple sclerosis (MS) suggesting to “interpret with caution positiveimmunoglobulin G (IgG) index when testing for oligoclonal bands (OB) is negative or not performed”. Theaim of this study was to compare the performance of K and IgG indexes for MS diagnosis and OB detectionin a cohort of Italian patients. We enrolled 385 patients (127 MS, 258 non-MS) who had cerebrospinal fluid(CSF) analysis, including isoelectric focusing (IEF), to detect OB in the diagnostic work-up. Albumin, IgGand free light chains were measured by nephelometry and used to calculate IgG and K indexes. Althoughthe two markers were highly related (r = 0.75, r2 = 0.55, p < 0.0001), the K index showed greater sensitivity andnegative predictive value (versus the IgG index) for OB detection (97% versus 48% and 97% versus 71%) andMS diagnosis (96% versus 50% and 98% versus 78%). These results support K index (and not IgG index) as afirst-line marker for MS, followed by IEF, according to a sequential testing approach in CSF analysis.

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Epilepsy in Down Syndrome: A Highly Prevalent Comorbidity

Journal of Clinical Medicine ◽

10.3390/jcm10132776 ◽

2021 ◽

Vol 10 (13) ◽

pp. 2776

Author(s):

Miren Altuna ◽

Sandra Giménez ◽

Juan Fortea

Keyword(s):

Down Syndrome ◽

Functional Outcomes ◽

Clinical Presentation ◽

Late Onset ◽

Current Knowledge ◽

Epileptic Seizures ◽

Myoclonic Epilepsy ◽

Increased Risk ◽

Number Of Individuals

Individuals with Down syndrome (DS) have an increased risk for epilepsy during the whole lifespan, but especially after age 40 years. The increase in the number of individuals with DS living into late middle age due to improved health care is resulting in an increase in epilepsy prevalence in this population. However, these epileptic seizures are probably underdiagnosed and inadequately treated. This late onset epilepsy is linked to the development of symptomatic Alzheimer’s disease (AD), which is the main comorbidity in adults with DS with a cumulative incidence of more than 90% of adults by the seventh decade. More than 50% of patients with DS and AD dementia will most likely develop epilepsy, which in this context has a specific clinical presentation in the form of generalized myoclonic epilepsy. This epilepsy, named late onset myoclonic epilepsy (LOMEDS) affects the quality of life, might be associated with worse cognitive and functional outcomes in patients with AD dementia and has an impact on mortality. This review aims to summarize the current knowledge about the clinical and electrophysiological characteristics, diagnosis and treatment of epileptic seizures in the DS population, with a special emphasis on LOMEDS. Raised awareness and a better understanding of epilepsy in DS from families, caregivers and clinicians could enable earlier diagnoses and better treatments for individuals with DS.

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Primary leptomeningeal lymphoma masquerading as infectious tubercular meningitis

BMJ Case Reports ◽

10.1136/bcr-2021-243574 ◽

2021 ◽

Vol 14 (9) ◽

pp. e243574

Author(s):

Salini Sumangala ◽

Thidar Htwe ◽

Yousuf Ansari ◽

Lidia Martinez- Alvarez

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Correct Diagnosis ◽

Central Nervous System Lymphoma ◽

Final Diagnosis ◽

Csf Analysis ◽

Antitubercular Treatment ◽

Lymphoma Treatment ◽

Work Up ◽

Timely Treatment

Primary central nervous system lymphoma (PCNSL) is infrequent and often poses diagnostic conundrums due to its protean manifestations. We present the case of a South Asian young man presenting with raised intracranial pressure and a lymphocytic cerebrospinal fluid (CSF) with pronounced hypoglycorrhachia. Progression of the neuro-ophthalmic signs while on early stages of antitubercular treatment led to additional investigations that produced a final diagnosis of primary leptomeningeal lymphoma. Treatment with chemoimmunotherapy (methotrexate, cytarabine, thiotepa and rituximab (MATRix)) achieved full radiological remission followed by successful autologous transplant. This case highlights the difficulties and diagnostic dilemmas when PCNSL presents as a chronic meningeal infiltrative process. While contextually this CSF is most often indicative of central nervous system tuberculosis and justifies empirical treatment initiation alone, it is essential to include differential diagnoses in the investigation work-up, which also carry poor prognosis without timely treatment. High suspicion, multidisciplinary collaboration and appropriate CSF analysis were the key for a correct diagnosis.

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Combinations of Symptoms in Emergency Presentations: Prevalence and Outcome

Journal of Clinical Medicine ◽

10.3390/jcm8030345 ◽

2019 ◽

Vol 8 (3) ◽

pp. 345 ◽

Cited By ~ 5

Author(s):

Tobias Kuster ◽

Christian Nickel ◽

Mirjam Jenny ◽

Lana Blaschke ◽

Roland Bingisser

Keyword(s):

Time Course ◽

Predictive Power ◽

Secondary Analysis ◽

Clinical Work ◽

Adverse Outcomes ◽

University Hospital ◽

Chief Complaints ◽

The University ◽

Work Up ◽

Inclusion Period

The predictive power of certain symptoms, such as dyspnoea, is well known. However, research is limited to the investigation of single chief complaints. This is in contrast to patients in the emergency department (ED) presenting usually more than one symptom. We aimed to identify the most common combinations of symptoms and to report their related outcomes: hospitalisation, admission to intensive care units, and mortality. This is a secondary analysis of a consecutive sample of all patients presenting to the ED of the University Hospital Basel over a total time course of 6 weeks. The presence of 35 predefined symptoms was systematically assessed upon presentation. A total of 3960 emergency patients (median age 51, 51.7% male) were included. Over 130 combinations of two, 80 combinations of three, and 10 combinations of four symptoms occurred 42 times or more during a total inclusion period of 42 days. Two combinations of two symptoms were predictive for in-hospital mortality: weakness and fatigue (Odds ratio (OR) = 2.45), and weakness and headache (OR = 3.01). Combinations of symptoms were frequent. Nonspecific complaints (NSCs), such as weakness and fatigue, are among the most frequently reported combinations of symptoms, and are associated with adverse outcomes. Systematically assessing symptoms may add valuable information for prognosis and may therefore influence triage, clinical work-up, and disposition.

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Late onset epileptic seizures A retrospective study of 250 patients

Acta Neurologica Scandinavica ◽

10.1111/j.1600-0404.1985.tb00887.x ◽

2009 ◽

Vol 72 (4) ◽

pp. 380-384 ◽

Cited By ~ 19

Author(s):

José Luis Pérez López ◽

Jesús Longo ◽

Fernando Quintana ◽

Consuelo Diez ◽

José Berciano

Keyword(s):

Retrospective Study ◽

Late Onset ◽

Epileptic Seizures

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Comparison of immunotherapy and prognosis of seizures caused by viral encephalitis and autoimmune encephalitis

10.21203/rs.3.rs-496349/v1 ◽

2021 ◽

Author(s):

Xianjun Zhang ◽

Yanbing Han ◽

Xiaojuan Liu ◽

Wenqiu Yang ◽

Ting Wang ◽

...

Keyword(s):

Antiepileptic Drugs ◽

Lower Risk ◽

Yunnan Province ◽

Viral Encephalitis ◽

Autoimmune Encephalitis ◽

Seizure Outcome ◽

Acute Encephalitis ◽

Free Rate

Abstract Background: The immunotherapy that is more effective for seizures caused by viral encephalitis and autoimmune encephalitis and the long-term use of anti-epileptic drugs is not clear. We aimed to compare the immunotherapy and prognosis of seizures caused by viral encephalitis and autoimmune encephalitis.Methods: Clinical data of 121 patients with seizures caused by viral encephalitis and autoimmune encephalitis diagnosed and treated in the two largest tertiary general hospitals in the Yunnan Province were retrospectively collected to compare the immunotherapy used. Dynamic follow-up was performed to observe seizures and the use of antiepileptic drugs.Results: The seizure-free rates at 6 months and 12 months after the onset of viral encephalitis were 77.8% and 80.8%, respectively. In total, 79.1% of autoimmune encephalitis cases were seizure-free at 6 months after onset, and the seizure-free rate at 12 months was 91.9%. A total of 75.0% of viral encephalitis and 67.7% of autoimmune encephalitis patients discontinued antiepileptic drugs and were seizure-free at 12 months after onset. Patients with viral encephalitis treated with glucocorticoids alone had a lower risk of seizures after the acute phase than those treated with glucocorticoids combined with immunoglobulin (P < 0.05). The risk of seizures in patients with autoimmune encephalitis treated with glucocorticoids combined with immunoglobulin was lower than that in patients treated with glucocorticoids and immunoglobulin alone (P < 0.05).Conclusions: Immunotherapy may improve the seizure prognosis of patients with acute encephalitis. The prognosis of seizures due to viral encephalitis may be determined as early as 6 months after onset, while the seizure outcome of autoimmune encephalitis is further improved 12 months after onset.

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Neurological Presentation of Severe Dengue in Children From a Colombian Hyperendemic Area

10.21203/rs.3.rs-51332/v1 ◽

2020 ◽

Author(s):

Jaime E. Castellanos ◽

Paula Esteban ◽

Juanita Panqueba-Salgado ◽

Daniela Benavides-del-Castillo ◽

Valentina Pastrana ◽

...

Keyword(s):

Fungal Infections ◽

Hypovolemic Shock ◽

University Hospital ◽

Severe Dengue ◽

Laboratory Findings ◽

Dengue Disease ◽

Neurological Signs ◽

Csf Analysis ◽

Neurological Patients ◽

The University

Abstract Objective: Dengue transmission is sustained in Colombia with increasing prevalence mainly in children. This work was aimed to describe a cases series of children diagnosed with dengue presenting neurological disease in the Huila province of Colombia. Eleven pediatric febrile patients confirmed to dengue disease and presenting neurological signs were studied in the University Hospital of Neiva, Huila province. Clinical and laboratory findings, CSF cytochemical analysis, neurology images, and serology and molecular studies were performed. Results. Viral RNA was detected in all patients’ sera by RT-PCR. Nine out of 11 were primary infections. Tonic-clonic seizures (73%), consciousness alterations (27%), irritability (27%) and ataxia (18%) were the most frequent neurological signs. None of the patients had plasma leakage, hypovolemic shock or liver disease, confirming the encephalitis diagnosis. Diagnostic images did not show abnormal findings neither bacterial or fungal infections were detected in CSF analysis. All patients survived without sequelae except in one patient that presented ataxia for months. In conclusion, we described a group of children with neurological signs during severe dengue disease as the main finding, indicating the importance of include dengue as a differential diagnosis in neurological patients from endemic areas.

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A Septuagenarian With Progressive Hemiparesis

10.1093/med/9780197583425.003.0015 ◽

2021 ◽

pp. 48-50

Author(s):

Roman Kassa ◽

B. Mark Keegan

Keyword(s):

Multiple Sclerosis ◽

Late Onset ◽

Progressive Multiple Sclerosis ◽

Oligoclonal Bands ◽

Hyperintense Lesion ◽

Fluid Analysis ◽

Hemiparetic Gait ◽

Magnetic Resonance Imaging Mri ◽

Disease Modifying Agents ◽

The Right

A 78-year-old man with no pertinent medical history sought care for an 18-month history of progressive right lower extremity weakness, gait impairment, and falls. On neurologic examination, he had a hemiparetic gait. He had normal higher cognitive function and cranial nerve function. Motor examination showed decreased bulk over the right hand with no fasciculations, mild spasticity over the right leg, and right hemiparesis with an upper motor neuron pattern. Deep tendon reflexes were brisk throughout his limbs, and he had an extensor plantar reflex on the right side. He had impaired vibratory sense at the toes, with otherwise normal sensory and coordination examinations. Magnetic resonance imaging (MRI) of the brain showed ovoid periventricular and punctate subcortical and deep white matter T2 hyperintense foci. Some of these had corresponding T1 hypointensity. MRI of the cervical spine showed 1 eccentrically located T2 hyperintense lesion over the right lateral aspect of C2. Cerebrospinal fluid analysis showed no pleocytosis, an increased protein concentration of 66 mg/dL, and 4 unique oligoclonal bands. A diagnosis of primary progressive multiple sclerosis, very late onset, was made. With any diagnosis of late-onset multiple sclerosis, a decision about whether multiple sclerosis disease-modifying agents are indicated should be carefully considered. Our older patient had a progressive disease course, and neuroimaging studies did not reveal evidence of active disease. Based on this, a decision was made to monitor him clinically and radiologically. Management of spasticity with regular daily stretching exercises was discussed with him. A first clinical manifestation of multiple sclerosis can occur at a later-than-typical age. Most studies consider an onset at age 50 years or older to be late-onset multiple sclerosis, whereas first symptoms occurring at age 60 years or older are commonly referred to as very late–onset MS.

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Astrocyte and Neuronal Pannexin1 Contribute Distinctly to Seizures

ASN NEURO ◽

10.1177/1759091419833502 ◽

2019 ◽

Vol 11 ◽

pp. 175909141983350 ◽

Cited By ~ 6

Author(s):

Eliana Scemes ◽

Libor Velíšek ◽

Jana Velíšková

Keyword(s):

Atp Release ◽

Epileptic Seizures ◽

Immunohistochemical Analysis ◽

Adenosine Kinase ◽

Seizure Outcome ◽

Release Channel ◽

Extracellular Adenosine ◽

Targeted Deletion ◽

Acute Seizures ◽

Opposing Effects

ATP- and adenosine-mediated signaling are prominent types of glia–glia and glia–neuron interaction, with an imbalance of ATP/adenosine ratio leading to altered states of excitability, as seen in epileptic seizures. Pannexin1 (Panx1), a member of the gap junction family, is an ATP release channel that is expressed in astrocytes and neurons. Previous studies provided evidence supporting a role for purinergic-mediated signaling via Panx1 channels in seizures; using mice with global deletion of Panx1, it was shown that these channels contribute in maintenance of seizures by releasing ATP. However, nothing is known about the extent to which astrocyte and neuronal Panx1 might differently contribute to seizures. We here show that targeted deletion of Panx1 in astrocytes or neurons has opposing effects on acute seizures induced by kainic acid. The absence of Panx1 in astrocytes potentiates while the absence of Panx1 in neurons attenuates seizure manifestation. Immunohistochemical analysis performed in brains of these mice, revealed that adenosine kinase (ADK), an enzyme that regulates extracellular levels of adenosine, was increased only in seized GFAP-Cre:Panx1f/f mice. Pretreating mice with the ADK inhibitor, idotubercidin, improved seizure outcome and prevented the increase in ADK immunoreactivity. Together, these data suggest that the worsening of seizures seen in mice lacking astrocyte Panx1 is likely related to low levels of extracellular adenosine due to the increased ADK levels in astrocytes. Our study not only reveals an unexpected link between Panx1 channels and ADK but also highlights the important role played by astrocyte Panx1 channels in controlling neuronal activity.

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