Extratemporal Involvement Research Articles

Mesiotemporal Volumetry, Cortical Thickness, and Neuropsychological Deficits in the Long-term Course of Limbic Encephalitis.

Limbic encephalitis (LE) is an autoimmune disease often associated with temporal lobe epilepsy and subacute memory deficits. It is categorized into serologic subgroups, which differ in clinical progress, therapy response, and prognosis. Using longitudinal MRI analysis, we hypothesized that mesiotemporal and cortical atrophy rates would reveal serotype-specific patterns and reflect disease severity. In this longitudinal case-control study, all individuals with antibody-positive (glutamic acid decarboxylase 65 [GAD], leucine-rich glioma-inactivated protein 1 [LGI1], contactin-associated protein 2 [CASPR2], and N-methyl-d-aspartate receptor [NMDAR]) nonparaneoplastic LE according to Graus' diagnostic criteria treated between 2005 and 2019 at the University Hospital Bonn were enrolled. A longitudinal healthy cohort was included as the control group. Subcortical segmentation and cortical reconstruction of T1-weighted MRI were performed using the longitudinal framework in FreeSurfer. We applied linear mixed models to examine mesiotemporal volumes and cortical thickness longitudinally. Two hundred fifty-seven MRI scans from 59 individuals with LE (34 female, age at disease onset [mean ± SD] 42.5 ± 20.4 years; GAD: n = 30, 135 scans; LGI1: n = 15, 55 scans; CASPR2: n = 9, 37 scans; and NMDAR: n = 5, 30 scans) were included. The healthy control group consisted of 128 scans from 41 individuals (22 female, age at first scan [mean ± SD] 37.7 ± 14.6 years). The amygdalar volume at disease onset was significantly higher in individuals with LE (p ≤ 0.048 for all antibody subgroups) compared with that in healthy controls and decreased over time in all antibody subgroups, except in the GAD subgroup. We observed a significantly higher hippocampal atrophy rate in all antibody subgroups compared with that in healthy controls (all p ≤ 0.002), except in the GAD subgroup. Cortical atrophy rates exceeded normal aging in individuals with impaired verbal memory, while those who were not impaired did not differ significantly from healthy controls. Our data depict higher mesiotemporal volumes in the early disease stage, most likely due to edematous swelling, followed by volume regression and atrophy/hippocampal sclerosis in the late disease stage. Our study reveals a continuous and pathophysiologically meaningful trajectory of mesiotemporal volumetry across all serogroups and provides evidence that LE should be considered a network disorder in which extratemporal involvement is an important determinant of disease severity.

Paraneoplastic and non-paraneoplastic limbic encephalitis: distinguishing features and outcomes (P7-5.031)

Paraneoplastic and non-paraneoplastic limbic encephalitis: distinguishing features and outcomes (P7-5.031)

Inferior fronto-occipital fascicle displacement in temporoinsular gliomas using diffusion tensor imaging.

Background and PurposeBrain tumors can result in displacement or destruction of important white matter tracts such as the inferior fronto‐occipital fascicle (IFOF). Diffusion tensor imaging (DTI) can assess the extent of this effect and potentially provide neurosurgeons with an accurate map to guide tumor resection; analyze IFOF displacement patterns in temporoinsular gliomas based on tumor grading and topography in the temporal lobe; and assess whether these patterns follow a predictable pattern, to assist in maximal tumor resection while preserving IFOF function.MethodsThirty‐four patients with temporal gliomas and available presurgical MRI were recruited. Twenty‐two had insula infiltration. DTI deterministic region of interest (ROI)‐based tractography was performed using commercial software. Tumor topographic imaging characteristics analyzed were as follows: location in the temporal lobe and extent of extratemporal involvement. Qualitative tractographic data obtained from directional DTI color maps included type of involvement (displaced/edematous‐infiltrated/destroyed) and displacement direction. Quantitative tractographic data of ipsi‐ and contralateral IFOF included whole tract volume, fractional anisotropy, and fractional anisotropy of a 2‐dimensional coronal ROI on the tract at the point of maximum tumor involvement.ResultsThe most common tract involvement pattern was edematous/infiltrative displacement. Displacement patterns depended on main tumor location in the temporal lobe and presence of insular involvement. All tumors showed superior displacement pattern. In lateral tumors, displacement tendency was medial. In medial tumors, displacement tendency was lateral. When we add insular involvement, the tendency was more medial displacement. A qualitative and quantitative assessment supported these results.ConclusionsIFOF displacement patterns are reproducible and suitable for temporoinsular gliomas presurgical planning.

Giant Facial Nerve Schwannoma with Extra-Temporal Involvement: A Series Of Two Cases.

Facial nerve schwannoma is a rare benign tumor of temporal bone arising from the schwann cells with incidence of 0.8%. They can arise from any segment of facial nerve with geniculate ganglion being the most common and labyrinthine segment the second commonest site. Intra-temporal location is common while only 9% of the cases have extra-temporal or parotid gland involvement. Bony remodeling or scalloping of the facial canal and the surrounding bone is the classic radiological feature of schwannoma. However schwannomas of temporal bone location can show bony erosions. The management option depends on site, extent, facial nerve function and hearing status. Surgery is reserved for large tumors with poor facial functions, hearing loss and giddiness. Giant facial nerve schwannoma with extra-temporal involvement is a rare entity with only handful number of cases reported in the literature. We present a series of two cases of giant facial nerve schwannoma with parotid gland involvement.

Polyradiculitis in autoimmune encephalitis: a case report and review

BackgroundLimbic encephalitis is a subacute progressive disorder characterized by disturbances in memory and behavior along with seizures. Antibodies against leucine-rich glioma-inactivated 1 (LGI1) are associated with a subtype of encephalitis which along with the abovementioned symptoms is also characterized by severe pain and autonomic dysfunction. The classical radiological presentation of LGI1 encephalitis is that of amygdala and hippocampal enlargement unilaterally or bilaterally with a T2 hyperintensity. Extratemporal involvement is considered a rare feature.Case descriptionWe present the only known case in our knowledge of anti-LGI1 encephalitis in a 47-year-old male presenting as dorsal root ganglia and spinal nerve enhancement on imaging.DiscussionClinicians should be aware of this atypical presentation and consider anti-LGI1 encephalitis as a possible diagnosis when presented with such a neuroradiological feature.

Prognostic significance of subsequent extra-temporal involvement in cryptogenic new onset refractory status epilepticus (NORSE) initially diagnosed with limbic encephalitis

IntroductionNew-onset refractory status epilepticus (NORSE) is defined as refractory SE in patients without active epilepsy or relevant neurological disorder with no clear active causes. Diverse types and etiologies of NORSE are reported in various groups. Limbic encephalitis (LE) is reported as one of etiologies of NORSE. In this study, we investigated whether there were any intersections between NORSE and limbic encephalitis, as well as the presence of prognostic factors in intersection patients. MethodsWe retrospectively analyzed patients who met both the definition of NORSE and diagnostic criteria of LE at the initial presentation from our database. Clinical characteristics and blood test, cerebrospinal fluid, electroencephalography, and magnetic resonance imaging results were reviewed. Prognosis was recorded as ICU admission stay, total length of hospitalization, and modified Rankin Scale at discharge. In particular, we determined which factors were associated with patients’ prognosis. ResultsThirteen patients were selected. Nine of the 13 patients had myalgia and 8 patients had fever in the prodromal period. Twelve of the 13 patients had acute memory impairment or confusion before SE development. In addition, 46.2% of the patients showed leukopenia or thrombocytopenia. Median body temperature at hospital arrival was 37.6 °C. Nine patients showed generalized tonic-clonic SE. All patients were treated with immunotherapy and 11 of the 13 patients achieved burst suppression through induced coma therapy. Ten patients showed lesion extension on follow-up imaging. The most common extension site was the claustrum. Patients with more lesion extension showed poorer outcomes than those without lesion extension. ConclusionSubsequent extratemporal lesion extension was closely associated with poor prognosis in NORSE-LE patients. This study explores a new subtype of NORSE and suggests a possible common underlying pathomechanism between NORSE and LE.

The Natural History of Facial Schwannomas: A Meta-Analysis of Case Series.

Objective This study is to establish predictors of facial paralysis and auditory morbidity secondary to facial schwannomas by assimilating individualized patient data from the literature. Design A systematic review of the literature was conducted for studies regarding facial schwannomas. Studies were only included if they presented patient level data, House-Brackmann grades, and tumor location by facial nerve segment. Odds ratios (OR) were estimated using generalized linear mixed models. Main Outcome Measures Facial weakness and hearing loss. Results Data from 504 patients were collected from 32 studies. The geniculate ganglion was the most common facial nerve segment involved (39.3%). A greater number of facial nerve segments involved was positively associated with both facial weakness and hearing loss, whereas tumor diameter did not correlate with either morbidity. Intratemporal involvement was associated with higher odds of facial weakness (OR = 4.78, p < 0.001), intradural involvement was negatively associated with facial weakness (OR = 0.56, p = 0.004), and extratemporal involvement was not a predictor of facial weakness (OR = 0.68, p = 0.27). The odds of hearing loss increased with more proximal location of the tumor (intradural: OR = 3.26, p < 0.001; intratemporal: OR = 0.60, p = 0.14; extratemporal: OR = 0.27, p = 0.01). Conclusion The most important factors associated with facial weakness and hearing loss are tumor location and the number of facial nerve segments involved. An understanding of the factors that contribute most heavily to the natural morbidity can help guide the appropriate timing and type of intervention in future cases of facial schwannoma.

Auras as a prognostic factor in anterior temporal lobe resections for mesial temporal sclerosis.

Anterior temporal lobectomy for mesial temporal sclerosis (MTS) is a very effective measure for the control of seizures, and the probability of becoming seizure-free is approximately 70-90%. However, 30% of patients still experience seizures after surgery. An aura is a subjective ictal phenomenon that may precede an observable seizure. However, there are few studies on the prognostic factor aura although, being the initial symptoms of epileptic seizures, many types of auras have significant localizing or lateralizing value. This study hypothesized that the type of pre-operative aura may predict the post-surgical outcome in patients with medically refractory temporal lobe epilepsy due to MTS. Of 1214 patients evaluated for surgery in the Epilepsy Center of Faculdade de Medicina de São Jose do Rio Preto (FAMERP), a tertiary Brazilian epilepsy center, 400 underwent anterior temporal lobectomy (ATL) for MTS. The number and type of auras were analyzed and compared with the Engel classification for outcome. Analyzing the patients by the type of aura, those who had extratemporal auras had the worst post-surgical result according to the Engel classification. Although mesial auras are apparently a good prognostic factor, patients without aura also had a worse prognosis. There were no differences between simple and multiple auras. To identify the most appropriate candidates for ATL, it is very important to consider the favorable prognostic factors for counseling patients in daily practice. Patients with symptoms and clinical signs that suggest extratemporal involvement may have unfavorable outcomes.

Description of Ictal HFO Mapping in Patients with Both Temporal and Extratemporal Seizure Focus.

Objective. Review presurgical use of ictal HFO mapping to detect ictal activation areas with dual seizure focus in both the temporal and extratemporal cortex. Methods. Review of consecutive patients admitted to the University of South Alabama Epilepsy Monitoring Unit (SouthCEP) between January 2014 and October 2015, with suspected temporal lobe epilepsy and intracranial electrode recording. Ictal HFO localization was displayed in 3D reconstructed brain images using the patient's own coregistered magnetic resonance imaging (MRI) and computed tomography (CT) with the implanted electrodes. Results. Four of fifteen patients showed evidence of extratemporal involvement at the onset of the clinical seizures. Ictal HFO mapping involving both frontal and temporal lobe changed the surgical resection areas in three patients where the initial surgical plan included only the temporal lobe. Resection of the ictal HFO at the onset of the seizure and the initial propagation region was associated with seizure freedom in all patients; follow-up period ranged from 12 to 25 months. Significance. Extratemporal ictal involvement may not have clinical manifestations and may account for surgical failure in temporal lobe epilepsy. Ictal HFO mapping is useful to define the ictal cortical network and may help detect an extratemporal focus.

Do You Know of Cases of Wernicke’s Aphasia Post Herpes Simples Viral Encephalitis?

This editorial is a request for clinician researchers to report on speech recovery in cases of Wernicke’s Aphasia post Herpes Simplex Viral Encephalitis. The literature, while it contains detailed case histories of Wernicke’s cases post stroke, does not contain extensive material on speech recovery post encephalitis. A case report is now in progress, but there is little current and detailed literature in which to compare the clients progress. What is clear in the literature is the etiology of the disorder Herpes Simplex Virus Type 1 (HSV-1), along with HSV-2, are neurotropic members of the Herpesviridae family. HSV-1 most commonly causes cold sores but can also lead to genital herpes infections, while HSV-2 predominately causes genital herpes. Transmission occurs via mucosal surfaces including the oral and respiratory surfaces or through compromised skin, such as by sharing drinking vessels or utensils, kissing, and other high-risk skin-to-skin contact. HSV-1 is usually contracted during infancy or childhood through exposure to an infected adult. Transmission does not require an active infection or visible sores and can be spread through asymptomatic viral shedding [1,2]. There is a high seroprevalence in the general population, with an estimated 70~90% of asymptomatic individuals harboring the HSV-1 [3,4]. There is currently no cure for HSV but symptoms can be managed with antiviral medications [5]. Exactly how HSV-1 infiltrates the central nervous system to cause to HSE is greatly debated, with the olfactory bulb and trigeminal ganglia implicated in mice models [6]. The olfactory pathway is the most likely avenue of infection, as recurrent herpes labialis, which occurs in the trigeminal ganglia, rarely leads to HSE [7]. HSE normally affects the temporal lobe, which is responsible for retention of visual memory, language comprehension, processing of sensory input, and emotion. Therefore, symptoms of HSE include aphasia, confusion, and behavioral changes there can also be extratemporal involvement, including the frontal and parietal lobes, with an estimated 16% of patients with HSE having extratemporal infections [8]. This localization of infection is thought to be caused by the proximity of the temporal lobe to the olfactory bulb or trigeminal nerve [9] or preference of HSV for limbic cortices. Briefly, HSV-1 causes degeneration of cell nuclei and loss of plasma membranes, leading to multi-nucleated giant cells. This in turn causes inflammation, hemorrhaging, and eventual tissue necrosis and liquefaction [10].

Auras in temporal lobe epilepsy with hippocampal sclerosis: Relation to seizure focus laterality and post surgical outcome

We examined the relationship between presence and frequency of different types of auras and side of lesion and post surgical outcomes in 205 patients with medically intractable mesial temporal lobe epilepsy (MTLE) with unilateral hippocampal sclerosis (HS). With respect to the number of auras, multiple auras were not associated with side of lesion (p=0.551). The side of HS was not associated with the type of auras reported. One hundred fifty-seven patients were operated. The occurrence of multiple auras was not associated with post-surgical outcome (p=0.740). The presence of extratemporal auras was significantly higher in patients with poor outcome. In conclusion, this study suggests that the presence of extratemporal auras in patients with MTLE-HS possibly reflects extratemporal epileptogenicity in these patients, who otherwise showed features suggestive of TLE. Therefore, TLE-HS patients undergoing pre-surgical evaluation and presenting clinical symptoms suggestive of extratemporal involvement should be more extensively evaluated to avoid incomplete resection of the epileptogenic zone.

Temporal and Pontine Involvement in a Case of Herpes Simplex Encephalitis, Presenting as Kluver Bucy Syndrome - A Case Report

Bilateral temporal and frontal lobe involvement is a common characteristic of herpes simplex encephalitis (HSE). Clinical sequelae of herpes simplex encephalitis may manifest sometimes as Kluver Bucy syndrome (KBS). In herpes simplex encephalitis, apart from frontal lobe, extra temporal involvement is rare and uncommon. We report a case of HSE manifesting clinically as KBS with a rare radiological finding of temporal and extratemporal involvement of pons.

18F-FDG PET versus PET/CT as a diagnostic procedure for clinical suspicion of large vessel vasculitis

To the editor, FDG PET scintigraphy has been shown helpful in the diagnosis and follow-up of large vessel vasculitis, involving the aorta or its proximal branches, regardless of the precise nature of the vasculitis, either giant-cell arteritis (GCA) or Takayasu arteritis (TA) [1]. It was once thought that extratemporal involvement was more an exception than a rule; literature on FDG PET scintigraphy revealed that the aorta and its main branches are involved in more than half of the patients [2]. Due to the limited spatial resolution of PET (4–6 mm), it cannot reliably be used to diagnose inflammation of the temporal artery [3]. For those patients in whom the temporal artery biopsy and/or ultrasonography are negative, FDG PET/(CT) is, despite the expenses, a logical second approach. Patients with large vessel vasculitis present with vague symptoms of fatigue and malaise, weight loss and fever in the presence of raised inflammatory parameters, FDG PET/(CT) may directly point to large vessel vasculitis or to occult inflammatory or neoplastic disorders causing these symptoms . The diagnostic yield of FDG PET/(CT) in unexplained inflammatory disorders and unexplained febrile disorders are reported to be similar [4, 5]. The lack of data correlating PET findings with tissue evidence of large vessel vasculitis remains a major problem. In this perspective we read with interest the article of Lehmann et al., in which the diagnostic value of FDG PET was determined in 20 patients [6]. It is therefore disappointing that vasculitis was confirmed by histology in only 4 of the 20 investigated patients. In the other 16 patients, vasculitis was considered confirmed by pathologic findings in conventional as well as MRI angiography, and classified as either GCA if three of five American College of Rheumatology (ACR) criteria were fulfilled, or TA if three of the six ACR criteria for TA were fulfilled. The ACR criteria are reported to have a sensitivity of 90.5% and a specificity of 97.8% [7]. It needs to be mentioned in our opinion that these criteria are based on the diagnoses of advanced cases whereas the early phase of the disease does not fulfil the ACR criteria which results in a delayed diagnosis [8]. Also angiography has the disadvantage that the early metabolic changes of the disease may be missed and will also lead to a delay in diagnosis and treatment. This means that in 16 of 20 patients, FDG PETwith high sensitivity for early stages of vasculitis is compared to ACR criteria and imaging modalities both underestimating early stages of vasculitis. A critical remark may also be made towards the diversity of the patient population, only 12 of 20 patients had newly established vasculitis. Eight of 20 patients developed increased systemic inflammatory markers despite immunosuppressive therapy. Effectively this means that, in this specific study population, results for initial diagnosis in large vessel vasculitis are combined with results for therapy monitoring. This is problematic as increased vascular uptake may persist for several years despite treatment with H. Balink (*) Department of Nuclear Medicine, Medical Center Leeuwarden, Leeuwarden, The Netherlands e-mail: hans.balink@znb.nl

Extratemporal EEG and MRI findings in ANNA-1 (anti-Hu) encephalitis

Extratemporal involvement has been reported in ANNA-1 encephalitis, but the rate is unknown. EEG and MRI are used in the evaluation of these patients, but the relative value of each has not been determined. The study objectives were to measure the rate of extratemporal abnormalities, and to determine the relative value of MRI and EEG in an ANNA-1 encephalitis cohort. We selected from the neuroimmunology laboratory database ANNA-1 seropositive patients who underwent: (1) neurological evaluation at Mayo Clinic Rochester between 1990 and 2010 (2) comprehensive autoimmune paraneoplastic serological evaluation and (3) at least one EEG and MRI. Of 28 identified patients, the EEG was abnormal in 24 (86%). Extratemporal abnormalities included slowing [12 (43%)], epileptiform discharges [eight (29%)], and epilepsia partialis continua [two (7%)]. In ten patients, only the MRI or EEG showed an abnormality but not both. Six patients had focal EEG abnormalities localized to regions other than those on MRI. In 13 patients with a negative MRI, the EEG showed a focal abnormality in seven (54%). Extratemporal EEG abnormalities are present in nearly half of ANNA-1 seropositive patients, suggesting that extratemporal involvement is common. EEG and MRI are often complementary in determining lesional distribution in ANNA-1 seropositive patients.

Herpes Simplex Type 1 Encephalitis Restricted to the Brainstem in a Pediatric Patient

Herpes simplex encephalitis is a potentially fatal infection of central nervous system that typically involves frontal and temporal lobes. Occasionally, it presents an extratemporal involvement and in rarer cases, it is limited to the brainstem. We describe a case of an adolescent who presented with fever, sore throat, and vertigo. Clinical picture evolved to lethargy, tetraparesis, consciousness impairment, and respiratory failure. MRI showed lesions restricted to the brainstem. PCR of CSF was positive for herpes simplex type 1.

Unusual progression of herpes simplex encephalitis with basal ganglia and extensive white matter involvement

We report a 51-year old male with herpes simplex encephalitis (HSE) showing unusual progression and magnetic resonance (MR) findings. The initial neurological manifestation of intractable focal seizure with low-grade fever persisted for three days, and rapidly coma, myoclonic status, and respiratory failure with high-grade fever emerged thereafter. The polymerase chain reaction (PCR) result of cerebrospinal fluid (CSF) was positive for HSV-1 DNA. In the early stage, MR images (MRI) were normal. On subsequent MR diffusion-weighted (DW) and fluid-attenuated inversion recovery (FLAIR) images, high-intensity areas first appeared in the left frontal cortex, which was purely extra-temporal involvement, and extended into the basal ganglia, then the white matter, which are relatively spared in HSE. Antiviral therapy and immunosuppressive therapy did not suppress the progression of HSE, and finally severe cerebral edema developed into cerebral herniation, which required emergency decompressive craniectomy. Histological examination of a biopsy specimen of the white matter detected perivascular infiltration and destruction of basic structure, which confirmed non specific inflammatory change without obvious edema or demyelination. The present case shows both MR and pathological findings in the white matter in the acute stage of HSE.

Extra temporal involvement in herpes simplex encephalitis

Temporal lobe abnormalities on brain imaging have been described as strong evidence for herpes simplex encephalitis (HSE) in appropriate clinical settings. Extra temporal abnormalities are less well described in these patients. We retrospectively reviewed 20 patients of HSE and found extra temporal involvement in 11 (55%) patients. Three patients (15 %) had pure extra temporal abnormalities. Twelve patients (60%) had temporal lobe involvement, four patients (20%) had pure temporal lobe involvement and five patients (25%) had normal CT/MRI scans. Our study suggests that extra temporal involvement on brain imaging is common in HSE and in a significant minority of the patients this can even be the sole abnormality.