The role of the epilepsy monitoring unit in the investigation of patients with epilepsy and intellectual disabilities.

BACKGROUND: A significant proportion of the people with intellectual disabilities (ID) has epilepsy and lives in institutions. These patients tend to have atypical presentations of epileptic seizures with an increased risk of misdiagnoses. They often have drug-resistant epilepsy (DRE) requiring polypharmacy with increased risk of morbidity. The aim of this study was to determine the usefulness of Epilepsy Monitoring Unit (EMU) in the diagnosis and management of these patients. METHODS: This is a retrospective observational study of people with epilepsy and ID living in institutions that were admitted to the EMU at London Health Sciences Center (LHSC), from January 2014 to December 2016. RESULTS: Out of 1121 patients admitted to the EMU at the LHSC, 1.96% (N = 22) fulfilled the inclusion criteria for this study. The mean age was 34.5 years (interquartile range [IQR]: 28.8-53); 50%(N = 11) were female. Fourteen (63.6%) had generalized epilepsy. Six (27.3%) had a history of status epilepticus. The mean number of antiseizure medications (ASMs) in those patients was three (IQR: 2-4). Eight (36.4%) patients had severely impaired or no language skills and seven (31.8%) required wheelchair. Eleven (50%) had a mood disorder and seven (31.8%) of them were taking antipsychotic medications. The mean duration of admission duration was 6.6 days (IQR: 3.5-8.5). There was a clinical-electrographic correlation between the behavioral events and epileptic seizures in nineteen (86.4%) of the patients. CONCLUSIONS: Admission to the EMU provided an accurate characterization of transient events in people with ID and epilepsy with improvement in their medical management.

Experience on the use of Vagus Nerve Stimulation during pregnancy.

OBJECTIVE: Vagus Nerve Stimulation (VNS) is a neuromodulation device approved for the treatment of medically refractory epilepsy. Worldwide, only 35 cases of pregnancies that has been described. This study aims to continue to increase the limited knowledge of the use of VNS during pregnancy. METHODS: We interrogated the database of the Epilepsy program at Western University (1998-2018), and identified those patients who were implanted with VNS and became pregnant. RESULTS: From 114 patients implanted with VNS in our centre, four patients had a total of seven pregnancies. This is the first report with one woman implanted with VNS having three pregnancies. Three patients had genetic generalized epilepsy and one focal epilepsy due to periventricular nodular heterotopia. The median duration since implantation was 3.17 years (IQR: 1.33-4.33) and the output was 2.75 mA (IQR: 1.5-3.5). No modifications in stimulation settings were made in any patient during pregnancy. Three patients had obstetric complications, requiring c-sections. All babies were healthy, except one with intellectual disabilities of unclear severity. CONCLUSION: Our small sample suggests VNS could increase the obstetrical complications, but is likely safe for the fetus. However, a larger sample size should be collected to determine safety and potential teratogenicity of VNS.

Prognostic factors in patients with refractory idiopathic generalized epilepsy.

OBJECTIVE: Idiopathic generalized epilepsy (IGE) is an epileptic condition with good response to antiepileptic drugs (AED). Major syndromes are epilepsy with generalized tonic-clonic seizures (GTCS) alone, absence epilepsy and juvenile myoclonic epilepsy. However, clinical practice shows drug-resistant patients. Endpoint is to identify clinical features related with refractoriness in IGE and in its each individual syndrome. METHODS: We retrospectively collected 279 consecutive patients with IGE assessed in the Epilepsy Clinic of our institution. We defined drug-resistant epilepsy as a failure of adequate trials of 2 tolerated and appropriately chosen and used AED schedules. We classified patients in two groups: drug-resistant and drug-responsive. Clinical features were compared among these groups, in the whole IGE group as well as in each syndrome. RESULTS: There were 122 drug-resistant, 105 drug- responsive; 52 were undefined and excluded from the analysis. After multivariate analysis, early seizures onset (age <13), long-time epilepsy, several generalized seizure types, status epilepticus, EEG with generalized epileptiform activity, mainly polyspikes, and side effects with AED brought up as poor outcome factors. Additionally, 50.6% identified modifiable seizure triggers. Regarding syndromes, epilepsy with generalized tonic-clonic seizures alone had the same factors except several seizure types; presence of additional GTCS, polyspikes, history of AED side effects and psychiatric disorder were poor factors for absence epilepsy; only psychiatric comorbidity revealed significance in juvenile myoclonic epilepsy. SIGNIFICANCE: Refractoriness in IGE and its major syndromes is associated with clinical and electrographic parameters. Moreover, lifestyle advices from neurologists to the patients might help them to achieve a better seizure control.

Reversible and irreversible cranial MRI findings associated with status epilepticus.

OBJECTIVE: There is limited information on neuroimaging changes in status epilepticus (SE). The objective of this study was to characterize the abnormalities associated with SE in cranial MRI of patients with SE. METHODS: A retrospective review of our records from 2001 to 2010 identified 203 patients with SE. Magnetic resonance imaging (MRI) changes considered were not attributable to any neurological disorder. RESULTS: Ten patients who met the inclusion criteria were found to have significant abnormalities. Magnetic resonance imaging findings included increased T2 signal changes in the gray and/or white matter with corresponding diffusion-weighted imaging (DWI) abnormalities (n=9). Apparent diffusion coefficient (ADC) values were both reduced (n=3) and increased (n=3). Other findings included changes affecting one hemisphere, a perilesional and homologous region, hippocampal changes, and findings in the thalamus, basal ganglia, brain stem, and cerebellum. CONCLUSIONS: Magnetic resonance imaging changes were diffuse. Notably, MRI changes were found to involve the brain stem, cerebellum, basal ganglia, and thalamus. Magnetic resonance imaging changes in the latter areas have not been previously well described. In addition, MRI changes tended to evolve after 1week; therefore, serial MRI is recommended in order to follow and highlight the MRI changes related to the neuroanatomic involvement seen in status epilepticus.

Disruptions of functional connectivity in the default mode network of comatose patients.

OBJECTIVE: To evaluate the possible role of the default mode network (DMN) in consciousness and assess the diagnostic or prognostic potential of DMN connectivity measures in the assessment of a patient group lacking cognitive awareness. METHODS: DMN connectivity was established using independent component analysis of resting-state fMRI data in patients with reversible (n = 2) and irreversible (n = 11) coma following cardiac arrest and compared to healthy controls (n = 12). RESULTS: A present and intact DMN was observed in controls and those patients who subsequently regained consciousness, but was disrupted in all patients who failed to regain consciousness. CONCLUSIONS: The results suggest that the DMN is necessary but not sufficient to support consciousness. Clinically, DMN connectivity may serve as an indicator of the extent of cortical disruption and predict reversible impairments in consciousness.

Fusion and visualization of intraoperative cortical images with preoperative models for epilepsy surgical planning and guidance.

OBJECTIVE: During epilepsy surgery it is important for the surgeon to correlate the preoperative cortical morphology (from preoperative images) with the intraoperative environment. Augmented Reality (AR) provides a solution for combining the real environment with virtual models. However, AR usually requires the use of specialized displays, and its effectiveness in the surgery still needs to be evaluated. The objective of this research was to develop an alternative approach to provide enhanced visualization by fusing a direct (photographic) view of the surgical field with the 3D patient model during image guided epilepsy surgery. MATERIALS AND METHODS: We correlated the preoperative plan with the intraoperative surgical scene, first by a manual landmark-based registration and then by an intensity-based perspective 3D-2D registration for camera pose estimation. The 2D photographic image was then texture-mapped onto the 3D preoperative model using the solved camera pose. In the proposed method, we employ direct volume rendering to obtain a perspective view of the brain image using GPU-accelerated ray-casting. The algorithm was validated by a phantom study and also in the clinical environment with a neuronavigation system. RESULTS: In the phantom experiment, the 3D Mean Registration Error (MRE) was 2.43 ± 0.32 mm with a success rate of 100%. In the clinical experiment, the 3D MRE was 5.15 ± 0.49 mm with 2D in-plane error of 3.30 ± 1.41 mm. A clinical application of our fusion method for enhanced and augmented visualization for integrated image and functional guidance during neurosurgery is also presented. CONCLUSIONS: This paper presents an alternative approach to a sophisticated AR environment for assisting in epilepsy surgery, whereby a real intraoperative scene is mapped onto the surface model of the brain. In contrast to the AR approach, this method needs no specialized display equipment. Moreover, it requires minimal changes to existing systems and workflow, and is therefore well suited to the OR environment. In the phantom and in vivo clinical experiments, we demonstrate that the fusion method can achieve a level of accuracy sufficient for the requirements of epilepsy surgery.

Cortical reorganization following anterior temporal lobectomy in patients with temporal lobe epilepsy.

BACKGROUND: Functional MRI was used to study the impact of temporal lobe epilepsy (TLE) and anterior temporal lobectomy (ATL) on the cortical language network in patients with medically refractory TLE. METHODS: Nineteen patients with medically refractory TLE and 11 healthy control subjects were enrolled in this study. Ten patients underwent left ATL (mean age 35.2 +/- 3.8 years), and 9 underwent right ATL (mean age 35.9 +/- 2.6 years). The subjects silently generated verbs in response to a series of visually presented nouns inside the scanner. Correlation analysis was performed between the subjects' performance on the clinical language tests and their neural response in the a priori cortical regions. RESULTS: Preoperative data revealed that the patients with TLE showed increased neural activity in the right inferior frontal gyri (IFG) and middle frontal gyri (MFG). The right TLE patients demonstrated strong correlation between their language performance and the level of cortical activation within the typical language areas. However, such a correlation was absent in the left TLE patients. After the ATL surgery, the left TLE patients showed reduced activation in the left MFG and right IFG, whereas no difference was observed in the right TLE patients. In the right TLE patients, the correlation between language performance and neural response shifted from the typical language areas to the anterior cingulate cortex. CONCLUSION: This study demonstrates that the cortical language network is affected differently by the left and right temporal lobe epilepsy and is reorganized after anterior temporal lobectomy.

MR imaging-compatible electroencephalography electrode system for an epilepsy monitoring unit.

We studied the usefulness of an MR imaging-compatible electroencephalography (EEG) electrode system for continuous EEG recordings in our epilepsy monitoring unit (EMU) by comparing 100 consecutive patients with MR imaging-compatible and MR imaging-incompatible EEG recording electrodes who underwent MR imaging between 3:00 pm and 7:00 am. The MR imaging-compatible system captured seizures in 21/50 (42%) patients and clinically valuable new electrographic data in 13/50 (26%) patients during the study interval, whereas possible seizures were lost to recording in 19/50 (38%) patients in the MR imaging-incompatible system. EEG recording was comparable by both systems, but the nurses could disconnect and reconnect the patients to their electrode cables only in the MR imaging-compatible system during the study interval while the EEG technologists were off duty. This study shows that the MR imaging-compatible system could be used routinely for long-term monitoring of the patients in EMUs.

Irreversible brain injury following status epilepticus.

Described here is a patient with medically intractable generalized epilepsy who developed status epilepticus (SE) affecting his right cerebral hemisphere for about 48 hours, which led to irreversible injury to that hemisphere. His partial SE did not respond to the first-line therapies, repeated doses of midazolam, or continuous intravenous infusion of propofol. Extensive investigations failed to find a cause of his SE except for a low serum valproic acid. A minor trauma that he suffered 1 week prior to his SE was of questionable significance. Neurological examination, neuropsychological testing, electroencephalography, and magnetic resonance imaging all demonstrated striking abnormalities limited to the affected cerebral hemisphere that did not resolve with repeated testing. This case illustrates permanent focal brain injury following prolonged partial SE in a patient with previously known generalized seizure disorder.

Myoclonic status epilepticus following repeated oral ingestion of colloidal silver.

The authors report a case of a 71-year-old man who developed myoclonic status epilepticus and coma after daily ingestion of colloidal silver for 4 months resulting in high levels of silver in plasma, erythrocytes, and CSF. Despite plasmapheresis, he remained in a persistent vegetative state until his death 5.5 months later. Silver products can cause irreversible neurologic toxicity associated with poor outcome.

Aboriginals with multiple sclerosis: HLA types and predominance of neuromyelitis optica.

BACKGROUND: MS is common in people of northern European ethnicity who live in northern geographic areas; however, MS is rarely identified among aboriginal peoples living in the same areas. OBJECTIVES: To determine the prevalence, clinical features, HLA type, and viral infections associated with MS among aboriginals in Manitoba, Canada. METHODS: A retrospective study was performed in which the clinical features of all aboriginal patients with MS together with HLA type and human herpesvirus-6, HIV-1, human T-cell lymphotropic virus-1, and endogenous retrovirus associated with MS (MSRV) infections were analyzed and compared with results from nonaboriginal patients with MS. RESULTS: Seven aboriginals with MS were identified with a period prevalence among aboriginals of 40:100,000. Clinical features included relapsing-remitting (n = 6) or primary progressive (n = 1) phenotypes with aggressive disease courses and frequent involvement of optic nerves and spinal cord (n = 5) compared with nonaboriginal patients. Autopsy of one patient showed necrosis and eosinophil infiltrates in a cervical spinal cord lesion and a demyelinated optic nerve. Analysis of HLA alleles at the DRB1 and DQB1 loci indicated that the HLA types detected were common in aboriginals, but there were no HLA alleles previously associated with the development of MS. Analysis of the copy number of MSRV did not show differences among aboriginals and nonaboriginals with or without MS. CONCLUSIONS: Aboriginals of Algonkian background are at increased risk for an aggressive type of MS, resembling neuromyelitis optica, which is resistant to conventional MS treatments and occurs independently of HLA alleles previously associated with MS.

Paroxysmal dyskinesias in patients with HIV infection.

OBJECTIVE: To determine the clinical features of paroxysmal dyskinesias among HIV type 1 (HIV-1)-seropositive patients. BACKGROUND: Movement disorders have been associated with HIV infection, although the full spectrum of these disorders remains uncertain. METHODS: Six adult HIV-1-seropositive patients presenting with paroxysmal dyskinesias were identified. Each patient underwent metabolic, CSF, EEG, and neuroimaging studies. RESULTS: Mean age at onset was 34.5 years and five of six patients were AIDS defined. Dyskinesias were focal, multifocal, or hemidystonic in four patients and generalized in another two patients. Two of the six patients had paroxysmal kinesigenic dyskinesias and the remaining four patients had paroxysmal nonkinesigenic dyskinesias. Choreoathetosis (n = 3), myoclonus (n = 2), postural tremor (n = 5), and dysarthria (n = 3) were observed. Benzodiazepines appeared beneficial in three of six patients. Two patients with HIV-associated dementia and paroxysmal nonkinesigenic dyskinesia had a progressive course to death. Autopsy of a patient with paroxysmal nonkinesigenic dyskinesias revealed intense astrogliosis and loss of calbindin-positive neurons in the subcortical gray matter. CONCLUSIONS: Paroxysmal dyskinesias may present as a primary HIV-1-induced neurologic syndrome. The occurrence of paroxysmal dyskinesias is associated with neuronal injury and loss in the subcortical gray matter but the mechanism remains unknown.

Primary headaches in HIV-infected patients.

Headache in patients with human immunodeficiency virus (HIV) infection may indicate life-threatening illnesses such as opportunistic infections or neoplasms. Alternatively, such patients may develop benign self-limiting headaches. Hence, defining the various types of headache in these patients is essential for proper management. This study describes the clinical characteristics of primary headaches occurring in a group of HIV-infected patients. Of 115 patients seen from 1990 to 1996, 44 (38%) had headaches. Primary headaches were present in 29 (66%) patients and secondary causes were identified in 15 (34%). Among those with primary headaches, migraine occurred in 22 (76%), tension-type headache in 4 (14%), and cluster headache in 3 (10%) patients. Half of those with migraine (n=ll), 1 patient with tension-type headache, and 1 patient with cluster headache developed chronic daily headaches which were severe and refractory to conventional headache or antiretroviral therapy. We conclude that primary headaches in patients with HIV infection are: (1) the commonest type of headache; (2) may present for the first time in individuals with severe immunosuppression; (3) usually bear no relationship to antiretroviral drug therapy; (4) polypharmacy, depression, anxiety, and insomnia are commonly associated comorbidities; (5) frequently do not respond to conventional management and carry a poor prognosis; and (6) do not require neuroradiological and/or cerebrospinal fluid evaluations.

Neuropsychiatric systemic lupus erythematosus and the syndrome of inappropriate secretion of antidiuretic hormone: a case report with very late onset systemic lupus erythematosus.

The syndrome of inappropriate secretion of antidiuretic hormone (SIADH) associated with neuropsychiatric lupus (NP-SLE) is rare. We report a case of SIADH associated with the new onset of SLE in an 88-yr-old female. The unique features of this case include the extreme age of onset of SLE presenting with neuropsychiatric manifestations and positive antiribosomal P antibody titres. Both the NP manifestations of SLE and SIADH were highly correlated with the SLE disease activity. This case illustrates a novel presentation of NP-SLE with SIADH which may develop due to antibody-mediated hypothalamic dysfunction.

Parkinsonism with HIV infection.

We describe six patients with parkinsonism and another 10 patients with parkinsonian features with human immunodeficiency virus (HIV) infection. In 50% of these patients, the symptoms were precipitated by neuroleptics. In the remaining patients, no obvious cause other than HIV infection was identified. Discontinuation of the neuroleptics produced complete recovery in one patient and partial or no response in others. Rapid progression of parkinsonism was noted in two patients, one of whom was treated with high-dose zidovudine (AZT) and benztropine. We conclude that patients with AIDS are at risk of developing an akinetic parkinsonism which may be precipitated by the use of neuroleptics, response to treatment is variable, and parkinsonism may be another primary HIV-induced syndrome.